WorldWideScience

Sample records for lymphoid follicles induced

  1. Saccharomyces boulardii administration can inhibit the formation of gastric lymphoid follicles induced by Helicobacter suis infection.

    Science.gov (United States)

    Yang, Lin; Tian, Zi-Bin; Yu, Ya-Nan; Zhang, Cui-Ping; Li, Xiao-Yu; Mao, Tao; Jing, Xue; Zhao, Wen-Jun; Ding, Xue-Li; Yang, Ruo-Ming; Zhang, Shuai-Qing

    2017-01-01

    Helicobacter suis has a greater tendency to induce gastric mucosa-associated lymphoid tissue lymphoma compared with other Helicobacter species in humans and animals. Saccharomyces boulardii has been established as an adjunct to H. pylori eradication treatment, but the effect of S. boulardii administration alone on Helicobacter infection remains unclear. Here, we found that S. boulardii administration effectively decreased the bacterial load of H. suis and inhibited the formation of lymphoid follicles in the stomach post-infection. The levels of H. suis-specific immunoglobulin A (IgA) and secretory IgA in the gastric juice and small intestinal secretions and the production of mouse β-defensin-3 in the small intestinal secretions were significantly increased by S. boulardii administration at 12 weeks after H. suis infection. In addition, feeding with S. boulardii inhibited the expression of inflammatory cytokines and lymphoid follicle formation-related factors after H. suis infection. These results suggested that S. boulardii may be useful for the prevention and treatment of Helicobacter infection-related diseases in humans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Colonic lymphoid follicles associated with colonic neoplasms

    International Nuclear Information System (INIS)

    Glick, S.N.; Teplick, S.K.; Ross, W.M.

    1986-01-01

    The authors prospectively evaluated 62 patients over 40 years old in whom lymphoid follicles were demonstrated on double-contrast enema examinations. Eighteen patients (29%) had no current radiographic evidence of, or history of, colonic neoplasms. Forty-four patients (71%) had an associated neoplasm. Fourteen patients had associated colonic carcinoma, and ten patients had a history of a previously resected colon cancer. One patient had previously undergone resection for ''polyps.'' Twenty-two patients had an associated ''polyp.'' There were no clinical or radiographic features that could reliably distinguish the neoplastic from the nonneoplastic groups. However, lymphoid follicles in the left colon or diffusely involving the colon were more likely to be associated with a colonic neoplasm. Lymphoid follicles were almost always identified near a malignant lesion

  3. Superficially located enlarged lymphoid follicles characterise nodular gastritis.

    Science.gov (United States)

    Okamura, Takuma; Sakai, Yasuhiro; Hoshino, Hitomi; Iwaya, Yugo; Tanaka, Eiji; Kobayashi, Motohiro

    2015-01-01

    Nodular gastritis is a form of chronic Helicobacter pylori gastritis affecting the gastric antrum and characterised endoscopically by the presence of small nodular lesions resembling gooseflesh. It is generally accepted that hyperplasia of lymphoid follicles histologically characterises nodular gastritis; however, quantitative analysis in support of this hypothesis has not been reported. Our goal was to determine whether nodular gastritis is characterised by lymphoid follicle hyperplasia.The number, size, and location of lymphoid follicles in nodular gastritis were determined and those properties compared to samples of atrophic gastritis. The percentages of high endothelial venule (HEV)-like vessels were also evaluated.The number of lymphoid follicles was comparable between nodular and atrophic gastritis; however, follicle size in nodular gastritis was significantly greater than that seen in atrophic gastritis. Moreover, lymphoid follicles in nodular gastritis were positioned more superficially than were those in atrophic gastritis. The percentage of MECA-79 HEV-like vessels was greater in areas with gooseflesh-like lesions in nodular versus atrophic gastritis.Superficially located hyperplastic lymphoid follicles characterise nodular gastritis, and these follicles correspond to gooseflesh-like nodular lesions observed endoscopically. These observations suggest that MECA-79 HEV-like vessels could play at least a partial role in the pathogenesis of nodular gastritis.

  4. [Comparative study of lymphoid follicles in mucosa of pharynx and mucosal associated lymphoid tissues in paranasal sinuses].

    Science.gov (United States)

    Zhai, Weigang; Yao, Min; Chen, Jue

    2013-08-01

    To study the relationship between the lymphoid follicles in mucous membrane of pharynx and mucosal associated lymphoid tissues (MALT). Ten folliculi obtained from 10 patients of follicular pharyngitis and mucosa taken form 10 patients of paranasal sinusitis were fixed in neutral formalin and embedded in paraffin. Sections were prepared, stained by H. E and by immunohistochemical method staining with S-100,and observe by light microscopy. We observed the morphology of lymphoid follicles in mucous membrane of pharynx with MALT in mucosa of paranasal sinusitis as the contrast. Lymphoid follicles in mucosa of pharynx compared with MALT in the mucosa of paranasal sinuses, there was no mantle zone, no typical germinal center and no mucosal epithelium, immunological staining with S-100 was week. The lymphoid follicles in mucosa of pharynx does not belong to the MALT.

  5. Lymphoid follicles in children with Helicobacter pylori-negative gastritis

    Science.gov (United States)

    Broide, Efrat; Richter, Vered; Mendlovic, Sonia; Shalem, Tzippora; Eindor-Abarbanel, Adi; Moss, Steven F; Shirin, Haim

    2017-01-01

    Purpose The prevalence of Helicobacter pylori gastritis has been declining, whereas H. pylori-negative gastritis has become more common. We evaluated chronic gastritis in children with regard to H. pylori status and celiac disease (CD). Patients and methods Demographic, clinical, endoscopic, and histologic features of children who underwent elective esophagogastroduodenoscopy were reviewed retrospectively. Gastric biopsies from the antrum and corpus of the stomach were graded using the Updated Sydney System. H. pylori presence was defined by hematoxylin and eosin, Giemsa, or immunohistochemical staining and urease testing. Results A total of 184 children (61.9% female) met the study criteria with a mean age of 10 years. A total of 122 (66.3%) patients had chronic gastritis; 74 (60.7%) were H. pylori-negative. Children with H. pylori-negative gastritis were younger (p=0.003), were less likely to present with abdominal pain (p=0.02), and were mostly of non-Arabic origin (p=0.011). Nodular gastritis was found to be less prevalent in H. pylori-negative gastritis (6.8%) compared with H. pylori-positive gastritis (35.4%, pgastritis and lymphoid follicles were associated most commonly with H. pylori. Although less typical, lymphoid follicles were demonstrated in 51.3% of H. pylori-negative patients. The presence or absence of CD was not associated with histologic findings in H. pylori-negative gastritis. Conclusion Our findings suggest that lymphoid follicles are a feature of H. pylori-negative gastritis in children independent of their CD status. PMID:28860835

  6. [Histopathological Study of the Relationship between Lymphoid Follicles and Different Endoscopic Types of Nodular Gastritis].

    Science.gov (United States)

    Nagata, Takuo; Ishitake, Hisahito; Shimamoto, Fumio; Tamura, Tadamasa; Matsumura, Kazunori; Sumii, Masaharu; Nakai, Shirou

    2014-11-01

    Nodular gastritis is characterized histologically by hyperplasia and enlargement of lymphoid follicles in the lamina propria. With the objective of elucidating the relationship between different endoscopic types of nodular gastritis and lymphoid follicles, distributions of lymphoid follicles in the lamina propria were investigated in young gastric cancer patients with nodular gastritis. For the study, whole-mucosal step sectioning of each resected stomach was performed, the densities of lymphoid follicles of all specimens were measured microscopically, and the horizontal and depth distributions were calculated. For assessment in the horizontal direction, density distribution diagrams of lymphoid follicles were created. For assessment in the depth direction, the different endoscopic types of nodular gastritis were compared in the five different analysis sites. In the assessment of the horizontal distribution, no characteristic distribution tendencies were observed in either the granular type group or the scattered type group; however, it was found that areas with relatively high densities of lymphoid follicles generally coincided with the areas where nodular gastritis was observed endoscopically. These results suggested that hyperplasia and aggregation of lymphoid follicles in the lamina propria are involved at the sites where nodular gastritis is observed endoscopically. In the assessment of the depth distribution, lymphoid follicles tended to be more unevenly distributed in the upper lamina propria in the granular type group than in the scattered type at the three different analysis sites where nodular gastritis was observed endoscopically. These results suggested the possibility of a granular type characteristic.

  7. Isolated lymphoid follicles are not IgA inductive sites for recombinant Salmonella

    International Nuclear Information System (INIS)

    Hashizume, Tomomi; Momoi, Fumiki; Kurita-Ochiai, Tomoko; Kaminogawa, Shuichi; Hosono, Akira; Kataoka, Kosuke; Shinozaki-Kuwahara, Noriko; Kweon, Mi-Na; Yamamoto, Masafumi

    2007-01-01

    In this study, we investigated whether isolated lymphoid follicles (ILF) play a role in the regulation of intestinal IgA antibody (Ab) responses. The transfer of wild type (WT) bone marrow (BM) to lymphotoxin-α-deficient (LTα -/- ) mice resulted in the formation of mature ILF containing T cells, B cells, and FDC clusters in the absence of mesenteric lymph nodes and Peyer's patches. Although the ILF restored total IgA Abs in the intestine, antigen (Ag)-specific IgA responses were not induced after oral immunization with recombinant Salmonella expressing fragment C of tetanus toxin. Moreover, Ag-specific cell proliferation was not detected in the ILF. Interestingly, no IgA anti-LPS Abs were detected in the fecal extracts of LTα -/- mice reconstituted with WT BM. On the basis of these findings, ILF can be presumed to play a role in the production of IgA Abs, but lymphoid nodules are not inductive sites for the regulation of Ag-specific intestinal IgA responses to recombinant Salmonella

  8. The chemokines CCL11, CCL20, CCL21, and CCL24 are preferentially expressed in polarized human secondary lymphoid follicles.

    Science.gov (United States)

    Buri, Caroline; Gutersohn, Andreas; Hauser, Chantal; Kappeler, Andreas; Mueller, Christoph

    2004-10-01

    Chemokines regulate cellular trafficking to and from lymphoid follicles. Here, the distribution pattern of four CCL chemokines is defined by in situ hybridization in human lymphoid follicles from tonsils and lymph nodes (LNs) of newborns and adults. Cells expressing CCL11 (eotaxin) and CCL20 (Exodus) were preferentially located within follicles, while cells expressing CCL21 (secondary lymphoid-tissue chemokine) and CCL24 (eotaxin-2) mRNA were almost exclusively found in the perifollicular areas. Hence, the two CCR3-binding chemokines, CCL11 and CCL24, showed a mutually exclusive expression pattern in the intra- and extra-follicular areas, respectively. Chemokine gene expression paralleled follicular maturation: in tonsils, where approximately 80% of follicles are polarized, CCL11 and CCL20 mRNA-positive cells were detected more frequently than in lymph nodes from adults, where about half of follicles are non-polarized. No intrafollicular chemokine expression was detectable in the primary follicles from newborns. Extrafollicular cells expressing CCL21 and CCL24 were again more frequent in tonsils than in LNs from adults. The observed preferential presence of cells expressing CC chemokines in polarized human lymphoid follicles indicates that chemokines are not only instrumental in the induction of follicle formation, but may also be involved in their further differentiation.

  9. Endoscopic features of lymphoid follicles in Helicobacter pylori-associated chronic gastritis.

    Science.gov (United States)

    Hayashi, Seishu; Imamura, Jun; Kimura, Kiminori; Saeki, Shunichi; Hishima, Tsunekazu

    2015-01-01

    Small, round, yellowish-white nodules (YWN) are frequently observed in Helicobacter pylori-associated gastritis. The aim of the present study was to investigate the clinical significance of these YWN. Participants comprised 211 patients with H. pylori-associated gastritis, ranging in age from 23 to 86 years. YWN were detected in 23% of participants, more frequently in women (33%) than in men (12%; P gastritis, and represented histological lymphoid follicles. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

  10. Lymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3.

    Science.gov (United States)

    Kelsen, Steven G; Aksoy, Mark O; Georgy, Mary; Hershman, Richard; Ji, Rong; Li, Xiuxia; Hurford, Matthew; Solomides, Charalambos; Chatila, Wissam; Kim, Victor

    2009-05-01

    The mechanisms underlying formation of lung lymphoid follicles (LF) in chronic obstructive pulmonary disease (COPD) are unknown. The chemokine receptor CXCR3 regulates immune responses in secondary lymphoid structures elsewhere in the body and is highly expressed by Th1 lymphocytes in the airway in COPD. Because chemokine receptors control inflammatory cell homing to inflamed tissue, we reasoned that CXCR3 may contribute to LF formation in COPD. We assessed the expression of CXCR3 and its ligands (IP-10/CXCL10, Mig/CXCL9, and ITAC/CXCL11) by LF cells in never-smokers, smokers without COPD, and subjects with COPD. CXCR3, IP-10, Mig, and ITAC expression were assessed in lung sections from 46 subjects (never-smokers, smokers without COPD [S], and subjects with COPD in GOLD stages 1-4) by immunohistochemistry. CXCR3-expressing T cells (CD8+ or CD4+) and B cells (CD20+) were topographically distributed at the follicle periphery and center, respectively. The percentage of immunohistochemically identified CXCR3+ cells increased progressively while proceeding from S through GOLD 3-4 (P < 0.01 for GOLD 3-4 vs. S). Moreover, the number of CXCR3+ follicular cells correlated inversely with FEV(1) (r = 0.60). The CXCR3 ligands IP-10 and Mig were expressed by several cell types in and around the follicle, including CD68+ dendritic cells/ macrophages, airway epithelial cells, endothelial cells, and T and B cells. These results suggest that LF form in the COPD lung by recruitment and/or retention of CXCR3-expressing T and B lymphocytes, which are attracted to the region through production of CXCR3 ligands IP-10 and Mig by lung structural and follicular cells.

  11. Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

    Science.gov (United States)

    Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim

    2018-01-16

    Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  13. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    International Nuclear Information System (INIS)

    Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2015-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  14. Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE.

    Science.gov (United States)

    Hatfield, Julianne K; Brown, Melissa A

    2015-10-01

    Innate lymphoid cells are immune cells that reside in tissues that interface with the external environment and contribute to the first line defense against pathogens. However, they also have roles in promoting chronic inflammation. Here we demonstrate that group 3 ILCs, (ILC3s - CD45+Lin-IL-7Rα+RORγt+), are normal residents of the meninges and exhibit disease-induced accumulation and activation in EAE. In addition to production of the pro-inflammatory cytokines IL-17 and GM-CSF, ILC3s constitutively express CD30L and OX40L, molecules required for memory T cell survival. We show that disease-induced trafficking of transferred wild type T cells to the meninges is impaired in ILC3-deficient Rorc-/- mice. Furthermore, lymphoid tissue inducer cells, a c-kit+ ILC3 subset that promotes ectopic lymphoid follicle development, a hallmark of many autoimmune diseases, are reduced in the meninges of EAE-resistant c-kit mutant Kit(W/Wv) mice. We propose that ILC3s sustain neuroinflammation by supporting T cell survival and reactivation in the meninges. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity.

    Science.gov (United States)

    Eddens, Taylor; Elsegeiny, Waleed; Garcia-Hernadez, Maria de la Luz; Castillo, Patricia; Trevejo-Nunez, Giraldina; Serody, Katelin; Campfield, Brian T; Khader, Shabaana A; Chen, Kong; Rangel-Moreno, Javier; Kolls, Jay K

    2017-03-28

    Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid structure composed of highly organized T cell and B cell zones that forms in the lung in response to infectious or inflammatory stimuli. Here, we develop a model for fungal-mediated iBALT formation, using infection with Pneumocystis that induces development of pulmonary lymphoid follicles. Pneumocystis-dependent iBALT structure formation and organization required CXCL13 signaling. Cxcl13 expression was regulated by interleukin (IL)-17 family members, as Il17ra -/- , Il17rb -/- , and Il17rc -/- mice failed to develop iBALT. Interestingly, Il17rb -/- mice have intact Th17 responses, but failed to generate an anti-Pneumocystis Th2 response. Given a role for Th2 and Th17 immunity in iBALT formation, we demonstrated that primary pulmonary fibroblasts synergistically upregulated Cxcl13 transcription following dual stimulation with IL-13 and IL-17A in a STAT3/GATA3-dependent manner. Together, these findings uncover a role for Th2/Th17 cells in regulating Cxcl13 expression and provide an experimental model for fungal-driven iBALT formation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Follicle stimulating hormone alleviates radiation-induced degeneration of mouse ovarian follicles

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.J. [Hanyang Univ., Seoul (Korea, Republic of); Kim, J.K.; Chun, K.J.

    2000-05-01

    The present study was performed to analyze the influences of (FSH) follicle stimulating hormone and {gamma}-radiation on the morphological changes of ovarian follicles and serum concentrations of testosterone, and estradiol-17{beta} in prepubertal mice. Female mice (ICR strain, three weeks old) were irradiated with 8.33 Gy of {gamma}-ray and followed by a 5 IU i.p.-injection of FSH to know the effect of FSH on the ovarian follicles. Left ovaries were collected at 0 h, 1 d, and 2 d after irradiation or saline/ FSH injection. Another group was received 5 IU of FSH 2 hours before irradiation to analyze the changes of ovarian steroidogenic abilities. By the morphometrical analysis, the number of normal or atretic follicles was counted and the ratio of normal to atretic follicle numbers was calculated. The percentage of atretic follicles was significantly reduced by the treatment of FSH. In the case of the FSH-injected group, the cellular debris caused by radiation was engulfed by the immune cells and the neighboring granulosa cells within the follicles. In concurrence with the morphometric analysis, the changes of the serum concentrations (pg/ml) of testosterone (T) and estradiol (E{sub 2}) were determined by radioimmunoassays. The concentration of T was 336.8{+-}61.3 in the control mice. One day after irradiation, the concentration went up to 484.8{+-}80.0 in the irradiated group, and down to 243.5{+-}80.7 in the FSH-treated one. The concentration of E{sub 2} was 174.9{+-}15.0 in the control group. One day after irradiation, however, the concentration was decreased to 94.8{+-}19.8, and 155.9{+-}8.7 in the irradiated and FSH-treated group, respectively. The alleviation of the follicular degeneration by the treatment of FSH is closely related to the elimination of the cellular debris and to the activities of the steroidogenic enzymes. (Author)

  17. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    International Nuclear Information System (INIS)

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A.

    2016-01-01

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  18. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Mahalingam, Sharada, E-mail: mahalin2@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Gao, Liying, E-mail: lgao@uiuc.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Gonnering, Marni, E-mail: mgonne2@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Helferich, William, E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-03-15

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  19. Mapping the follicle-stimulating hormone-induced signalling networks

    Directory of Open Access Journals (Sweden)

    Pauline eGloaguen

    2011-10-01

    Full Text Available Follicle-stimulating hormone (FSH is a central regulator of male and female reproductive function. Over the last decade, there has been a growing perception of the complexity associated with FSH-induced cellular signalling. It is now clear that the canonical Gs/cAMP/PKA pathway is not the sole mechanism that must be considered in FSH biological actions. In parallel, consistent with the emerging concept of biased agonism, several examples of ligand-mediated selective signalling pathway activation by gonadotropin receptors have been reported. In this context, it is important to gain an integrative view of the signalling pathways induced by FSH and how they interconnect to form a network. In this review, we propose a first attempt at building topological maps of various pathways known to be involved in the FSH-induced signalling network. We discuss the multiple facets of FSH-induced signalling and how they converge to the hormone integrated biological response. Despite of their incompleteness, these maps of the FSH-induced signalling network represent a first step towards gaining a system-level comprehension of this hormone’s actions, which may ultimately facilitate the discovery of novel regulatory processes and therapeutic strategies for infertilities and non-steroidal contraception.

  20. Inhibition of Follicle-Stimulating Hormone-Induced Preovulatory Follicles in Rats Treated with a Nonsteroidal Negative Allosteric Modulator of Follicle-Stimulating Hormone Receptor1

    OpenAIRE

    Dias, James A.; Campo, Brice; Weaver, Barbara A.; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M.; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M.

    2013-01-01

    We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human F...

  1. Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration.

    Science.gov (United States)

    Qiu, Weiming; Lei, Mingxing; Zhou, Ling; Bai, Xiufeng; Lai, Xiangdong; Yu, Yu; Yang, Tian; Lian, Xiaohua

    2017-06-01

    Regeneration of hair follicles relies on activation of hair follicle stem cells during telogen to anagen transition process in hair cycle. This process is rigorously controlled by intrinsic and environmental factors. 12-o-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, accelerates reentry of hair follicles into anagen phase. However, it is unclear that how TPA promotes the hair regeneration. In the present study, we topically applied TPA onto the dorsal skin of 2-month-old C57BL/6 female mice to examine the activity of hair follicle stem cells and alteration of signaling pathways during hair regeneration. We found that refractory telogen hair follicles entered anagen prematurely after TPA treatment, with the enhanced proliferation of CD34-positive hair follicle stem cells. Meanwhile, we observed Akt signaling was activated in epidermis, hair infundibulum, bulge and hair bulb, and Wnt signaling was also activated after hair follicle stem cells proliferation. Importantly, after overexpression of DKK1, a specific Wnt signaling inhibitor, the accelerated reentry of hair follicles into anagen induced by TPA was abolished. Our data indicated that TPA-induced hair follicle regeneration is associated with activation of Akt and Wnt/β-catenin signaling.

  2. Follicles in gut-associated lymphoid tissues create preferential survival niches for follicular Th cells escaping Thy-1-specific depletion in mice.

    Science.gov (United States)

    Mihalj, Martina; Kellermayer, Zoltán; Balogh, Peter

    2013-07-01

    Although a substantial number of T cells may escape depletion following in vivo mAb treatment in patients undergoing immunosuppression, their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues have not been analyzed in detail. Here we investigated the survival of CD4(+) T cells immediately following anti-Thy-1 mAb treatment in mice. We found a preferential survival of CD4(+) T cells expressing Thy-1 antigen in the Peyer's patches (PP) and also in mesenteric lymph nodes (MLN), where the relative majority of the surviving CD4(+) T cells displayed CD44(high)/CD62L(-) phenotype corresponding to effector memory T-cell features. These CD4(+) T cells also expressed CXCR5 and PD-1 (programmed cell death-1) markers characteristic for follicular Th cells (TFH). We also demonstrate that the immediate survival of these cells does not involve proliferation and is independent of IL-7. Induction of germinal center formation in spleen enhanced while the dissolution of follicular architecture by lymphotoxin-β receptor antagonist treatment slightly reduced TFH survival. Our results thus raise the possibility that the follicles within PP and MLN may create natural support niches for the preferential survival of TFH cells of the memory phenotype, thus allowing their escape during T-cell depletion.

  3. The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2016-02-01

    Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI). Fisher 344 PND4 rat ovaries were cultured for 12, 24, 48 or 96 h in medium containing DMSO ± 60 μM PM or KU 55933 (48 h; 10 nM). PM-induced activation of DNA damage repair genes was observed as early as 12 h post-exposure. ATM, PARP1, E2F7, P73 and CASP3 abundance were increased but RAD51 and BCL2 protein decreased after 96 h of PM exposure. PKCδ deficiency reduced numbers of all follicular stages, but did not have an additive impact on PM-induced ovotoxicity. ATM inhibition protected all follicle stages from PM-induced depletion. In conclusion, the ovarian DNA damage repair response is active post-PM exposure, supporting that DNA damage contributes to PM-induced ovotoxicity. - Highlights: • PM exposure induces DNA damage repair gene expression. • Inhibition of ATM prevented PM-induced follicle depletion. • PKCδ deficiency did not impact PM-induced ovotoxicity.

  4. Expression and localization of VEGFR-2 in hair follicles during induced hair growth in mice.

    Science.gov (United States)

    Wu, Xian-Jie; Jing, Jing; Lu, Zhong-Fa; Zheng, Min

    2018-06-16

    Recently, VEGFR-2 has been detected not only in vascular and lymphatic endothelial cells but also in some non-vascular endothelial cells, particularly human hair follicles, sebaceous glands, and sweat glands. In addition, VEGFR-2 has been confirmed to play direct roles in hair follicle keratinocyte regulation beyond simply angiogenesis. To elucidate whether VEGFR-2 activation plays a role in hair follicle cycling regulation, immunofluorescence of VEGFR-2 expression was performed during hair cycling of the dorsum of the mouse induced by hair plucking. We observed that staining for VEGFR-2 in hair follicles during anagen II and IV was much stronger than during anagen VI, catagen and telogen. During anagen II, intense staining for VEGFR-2 was observed on the keratinocyte strands of the hair follicle. Subsequently, we detected intense staining for VEGFR-2 in the ORS, IRS and hair bulb during anagen IV. Moderate staining for VEGFR-2 was detected in the ORS and hair bulb, but staining was most intense in IRS during anagen VI. During catagen, staining for VEGFR-2 in the IRS remained intense, while staining in the ORS and hair bulb was significantly weakened and was negative in the dermal papilla. During telogen, we detected VEGFR-2 in germ cells, cap, and club hair adjoining the epidermis. In conclusion, VEGFR-2 was expressed on the hair follicles of the dorsum of the mouse and varied in expression on the mouse hair follicles during hair cycling, suggesting that VEGFR-2 may exert roles in hair cycle regulation in hair follicles on the dorsum of mice.

  5. Inhibition of follicle-stimulating hormone-induced preovulatory follicles in rats treated with a nonsteroidal negative allosteric modulator of follicle-stimulating hormone receptor.

    Science.gov (United States)

    Dias, James A; Campo, Brice; Weaver, Barbara A; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M

    2014-01-01

    We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human FSHR identified an additional nonsteroidal small molecule (ADX68692). Although ADX68692 behaved like ADX61623 in inhibiting production of cAMP and progesterone, it also inhibited FSH-induced estradiol in an in vitro rat granulosa primary cell culture bioassay. When immature, noncycling female rats were injected subcutaneously or by oral dosing prior to exogenous FSH administration, it was found that ADX68692 decreased the number of oocytes recovered from the ampullae. The estrous cycles of mature female rats were disrupted by administration by oral gavage of 25 mg/kg and 10 mg/kg ADX68692. In the highest dose tested (25 mg/kg), 55% of animals cohabited with mature males had implantation sites compared to 33% in the 10 mg/kg group and 77% in the control group. A surprising finding was that a structural analog ADX68693, while effectively blocking progesterone production with similar efficacy as ADX68692, did not block estrogen production and despite better oral availability did not decrease the number of oocytes found in the ampullae even when used at 100 mg/kg. These data demonstrate that because of biased antagonism of the FSHR, nonsteroidal contraception requires that both arms of the FSHR steroidogenic pathway must be effectively blocked, particularly estrogen biosynthesis. Thus, a corollary to these findings is that it seems reasonable to propose that the estrogen-dependent diseases such as endometriosis may benefit from inhibition of FSH action at the ovary using the FSHR

  6. Sphingosine-1-phosphate prevents chemotherapy-induced human primordial follicle death.

    Science.gov (United States)

    Li, Fang; Turan, Volkan; Lierman, Sylvie; Cuvelier, Claude; De Sutter, Petra; Oktay, Kutluk

    2014-01-01

    Can Sphingosine-1-phosphate (S1P), a ceramide-induced death pathway inhibitor, prevent cyclophosphamide (Cy) or doxorubicin (Doxo) induced apoptotic follicle death in human ovarian xenografts? S1P can block human apoptotic follicle death induced by both drugs, which have differing mechanisms of cytotoxicity. S1P has been shown to decrease the impact of chemotherapy and radiation on germinal vesicle oocytes in animal studies but no human translational data exist. Experimental human ovarian xenografting to test the in vivo protective effect of S1P on primordial follicle survival in the chemotherapy setting. The data were validated by assessing the same protective effect in the ovaries of xenografted mice in parallel. Xenografted mice were treated with Cy (75 mg/kg), Cy+S1P (200 μM), Doxo (10 mg/kg), Doxo+S1P or vehicle only (Control). S1P was administered via continuous infusion using a mini-osmotic pump beginning 24 h prior to and ending 72 h post-chemotherapy. Grafts were then recovered and stained with anti-caspase 3 antibody for the detection of apoptosis in primordial follicles. The percentage of apoptotic to total primordial follicles was calculated in each group. Both Cy and Doxo resulted in a significant increase in apoptotic follicle death in human ovarian xenografts compared with controls (62.0 ± 3.9% versus 25.7 ± 7.4%, P 0.05). The findings from the ovaries of the severe combined immunodeficient mice mirrored the findings with human tissue. The functionality of the rescued human ovarian follicles needs to be evaluated in future studies though the studies in rodents showed that rescued oocytes can result in healthy offspring. In addition, the impact of S1P on cancer cells should be further studied. S1P and its future analogs hold promise for preserving fertility by pharmacological means for patients undergoing chemotherapy. This research is supported by NIH's NICHD and NCI (5R01HD053112-06 and 5R21HD061259-02) and the Flemish Foundation for Scientific

  7. Effects of maturation-inducing hormone on heterologous gap junctional coupling in ovarian follicles of Atlantic croaker

    Science.gov (United States)

    Yoshizaki, G.; Patino, R.; Thomas, P.; Bolamba, D.; Chang, Xiaotian

    2001-01-01

    A previous ultrastructural study of heterologous (granulosa cell-oocyte) gap junction (GJ) contacts in ovarian follicles of Atlantic croaker suggested that these contacts disappear late during the process of resumption of oocyte meiosis. This observation suggested that, unlike scenarios proposed for a number of other species, uncoupling of GJ is not necessary for the onset of meiotic resumption in croaker follicles. However, the functionality of heterologous GJ contacts and the temporal association between maturation-inducing hormone (MIH)-induced changes in heterologous coupling and resumption of oocyte meiosis have not been examined in Atlantic croaker. These questions were addressed with a cell-cell coupling assay that is based on the transfer of a GJ marker, Lucifer Yellow, from oocytes to granulosa cells. Follicle-enclosed oocytes injected with Lucifer Yellow allowed transfer of the dye into the follicle cell layer, thus confirming that there is functional heterologous coupling between the oocyte and the granulosa cells. Dye transfer was observed in vitellogenic, full-grown/maturation-incompetent, and full-grown /maturation-competent follicles. Treatment of maturation-competent follicles with MIH caused a time-dependent decline in the number of follicles transferring dye. However, although GJ uncoupling in some of the follicles was observed before germinal vesicle breakdown (GVBD, index of meiotic resumption), about 50% of the follicles maintained the ability to transfer dye even after GVBD had occurred. Further, a known GJ inhibitor (phorbol 12-myristate 13-acetate) blocked heterologous GJ within a time frame similar to that seen with MIH but without inducing any of the morphological changes (including GVBD) associated with follicular maturation. In conclusion, uncoupling of heterologous GJ seems insufficient and unnecessary for the onset of meiotic resumption in ovarian follicles of Atlantic croaker. ?? 2001 Elsevier Science.

  8. Progesterone improves the maturation of male-induced preovulatory follicles in anoestrous ewes.

    Science.gov (United States)

    Adib, Achraf; Freret, Sandrine; Touze, Jean-Luc; Lomet, Didier; Lardic, Lionel; Chesneau, Didier; Estienne, Anthony; Papillier, Pascal; Monniaux, Danielle; Pellicer-Rubio, Maria-Teresa

    2014-10-01

    The first ovulation induced by male effect in sheep during seasonal anoestrus usually results in the development of a short cycle that can be avoided by progesterone priming before ram introduction. In elucidating the involvement of the hypothalamic-pituitary-gonadal axis in the occurrence of short cycles, the effects of progesterone and the time of anoestrus on the development of male-induced preovulatory follicles were investigated in anoestrous ewes using morphological, endocrine and molecular approaches. Ewes were primed with progesterone for 2 (CIDR2) or 12 days (CIDR12) and untreated ewes used as controls during early (April) and late (June) anoestrus. The duration of follicular growth and the lifespan of the male-induced preovulatory follicles were prolonged by ∼1.6 days in CIDR12 ewes compared with the controls. These changes were accompanied by a delay in the preovulatory LH and FSH surges and ovulation. Intra-follicular oestradiol concentration and mRNA levels of LHCGR and STAR in the granulosa and theca cells of the preovulatory follicles were higher in CIDR12 ewes than the control ewes. The expression of mRNA levels of CYP11A1 and CYP17A1 also increased in theca cells of CIDR12 ewes. CIDR2 ewes gave intermediate results. Moreover, ewes ovulated earlier in June than in April, without changes in the duration of follicular growth, but these effects were unrelated to the lifespan of corpus luteum. Our results give the first evidence supporting the positive effect of progesterone priming on the completion of growth and maturation of preovulatory follicles induced by male effect in seasonal anoestrous ewes, thereby preventing short cycles. © 2014 Society for Reproduction and Fertility.

  9. Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung.

    Science.gov (United States)

    Hwang, Ji Young; Randall, Troy D; Silva-Sanchez, Aaron

    2016-01-01

    Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

  10. EFFECT OF NIGELLA SATIVA ON NUMBER OF CYSTIC FOLLICLES IN LETROZOLE INDUCED POLYCYSTIC OVARIES IN MICE

    Directory of Open Access Journals (Sweden)

    Noreen Anwar

    2016-06-01

    Full Text Available Objective: To observe the protective effect of Nigella sativa on number of cystic follicles in Letrozole induced polycystic ovaries in mice. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Anatomy, Army Medical College in collaboration with National Institute of Health from Nov 2014 to Nov 2015. Material and Methods: Forty female BALB/c mice were selected and divided in four groups, each having 10 animals. Group A served as control and was given normal diet. Group B was given Letrozole at a dose of 1milligram/kilogram body weight. Group C was treated with Letrozole for eight weeks at a dose of 1milligram/kilogram body weight and Nigella sativa seeds powder at a dose of 10grams/kilogram body weight once daily starting at 22 day and continued up to eight weeks. Group D was treated with Letrozole for eight weeks at a dose of 1milligram/kilogram body weight and Nigella sativa oil at a dose of 4milliliter/kilogram body weight once daily starting at 22 day and continued up to eight weeks. Animals were dissected a day after last dose. Size, shape, color and consistency of ovary was observed. Right ovary was processed, embedded and stained for histological study. Number of cystic follicles were counted and noted. Results: Significant number of cystic follicles was observed in ovaries of animals of group B as compared to group A. While their number decreased significantly in group C and D as compared to group B. Conclusion: Nigella sativa seeds powder and its oil, both have a similar protective effect on histomorphology of ovary of polycystic ovarian syndrome (PCOS in mice by decreasing the number of cystic follicles.

  11. Classical swine fever virus induces pyroptosis in the peripheral lymphoid organs of infected pigs.

    Science.gov (United States)

    Yuan, Jin; Zhu, Mengjiao; Deng, Shaofeng; Fan, Shuangqi; Xu, Hailuan; Liao, Jiedan; Li, Peng; Zheng, Jingfang; Zhao, Mingqiu; Chen, Jinding

    2018-05-02

    Classical swine fever virus (CSFV) causes a highly lethal disease in pigs, which is characterized by immunosuppression. Leukopenia is known to be a possible mechanism of immunosuppression during CSFV infection. As a new and specialized form of cell death, pyroptosis is the key response of the innate immune system to pathogens, and is widely involved in the occurrence and development of infectious diseases. However, the relationship between CSFV and pyroptosis has not been explored. In this study, we investigated the occurrence of pyroptosis in pigs following CSFV infection. According to qRT-PCR assay results, the prevalence of this virus in peripheral lymphoid organs (tonsils, lymph nodes, and spleen) was much higher than that in other organs. Severe bleeding, necrosis, and a significant reduction in lymphocytes were found in the peripheral lymphoid organs of CSFV-infected pigs based on histological examination. In-depth studies showed that an increased ratio of deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells were present in the peripheral lymphoid organs of the CSFV-infected group according to immunohistochemistry. Meanwhile, the p10 subunit and activity of caspase-1, which is a regulator of pyroptosis, the N-terminal domain of gasdermin D, which is an executor of pyroptosis, and the cleavage and secretion of IL-1b, which is a product of pyroptosis were increased in the peripheral lymphoid organs of the CSFV-infected group. Together, these results demonstrated that pyroptosis is involved in CSFV-induced cell death in vivo, which provides a new understanding of the mechanism associated with lymphocyte depletion and immunosuppression in pigs infected with this virus. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

    Science.gov (United States)

    Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2016-06-01

    Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.

  13. Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

    Science.gov (United States)

    Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

    2011-01-01

    Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. Lymphoid tissue inducer cells: pivotal cells in the evolution of CD4 immunity and tolerance?

    Directory of Open Access Journals (Sweden)

    Peter John Lane

    2012-02-01

    Full Text Available Phylogeny suggests that the evolution of placentation in mammals was accompanied by substantial changes in the mammalian immune system: in particular lymph nodes and CD4 high affinity memory antibody responses co-evolved during the same period. Lymphoid tissue inducer cells (LTi are members of an emerging family of innate lymphoid cells (ILCs that are crucial for lymph node development, but our studies have indicated that they also play a pivotal role in the long-term maintenance of memory CD4 T cells in adult mammals through their expression of the tumor necrosis family members, OX40- and CD30-ligands. Additionally, our studies have shown that these two molecules are also key operators in CD4 effector function, as their absence obviates the need for the FoxP3-dependent regulatory T cells (Tregs that prevent CD4 driven autoimmune responses. In this perspective article, we summarize findings from our group over the last 10 years, and focus specifically on the role of LTi in thymus. We suggest that like memory CD4 T cells, LTi also play a role in the selection and maintenance of the Tregs that under normal circumstances are absolutely required to regulate CD4 effector cells.

  15. Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice.

    Science.gov (United States)

    Comish, Paul B; Drumond, Ana Luiza; Kinnell, Hazel L; Anderson, Richard A; Matin, Angabin; Meistrich, Marvin L; Shetty, Gunapala

    2014-01-01

    Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT) and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP) is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1) mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2%) and to 80% in the male offspring of L1 (control value 33%). These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼ 70% of control and induced atrophic seminiferous tubules in ∼ 30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i) DNA damage is a common mechanism leading to induction of testicular cancer, ii) increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii) children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

  16. Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice.

    Directory of Open Access Journals (Sweden)

    Paul B Comish

    Full Text Available Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1 mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2% and to 80% in the male offspring of L1 (control value 33%. These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼ 70% of control and induced atrophic seminiferous tubules in ∼ 30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i DNA damage is a common mechanism leading to induction of testicular cancer, ii increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

  17. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

    Directory of Open Access Journals (Sweden)

    María Eugenia Hernandez

    2013-01-01

    Full Text Available Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily, chemical stress (hydrocortisone treatment, 50 mg/Kg weight, mixed stress (restraint plus hydrocortisone, or control treatment (without stress for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  18. RECTAL BIOPSY IN SHEEP AND GOATS FOR MONITORING AND ANTE-MORTEM DIAGNOSIS OF SCRAPIE: NUMBER OF LYMPHOID FOLLICLES IN TWO CONSECUTIVE COLLECTIONS

    Directory of Open Access Journals (Sweden)

    Helen Caroline Raksa

    2016-07-01

    O acúmulo da PrPSc em tecidos linfoides levou ao desenvolvimento de procedimentos de biopsia para o diagnóstico ante mortem da scrapie em ovinos, utilizando tecidos acessíveis como a tonsila(5 e terceira pálpebra(6, e a técnica de imuno-histoquímica (IHQ. Por outro lado, a grande área de folículos linfoides presente no reto de ovinos(7 tornou a biopsia retal uma possibilidade de diagnóstico ante mortem da scrapie. Amostras da mucosa retal têm sido colhidas e analisadas por meio de provas de IHQ para avaliar a presença de PrPSc no tecido linfoide associado à mucosa retoanal (RAMALT, do inglês Recto-Anal Mucosa Associated Lymphoid Tissue(8,9. No Brasil, o primeiro relato de scrapie foi em 1978, em um ovino Hampshire Down, importado da Inglaterra(10. Segundo a OIE, de 2008 a 2014 foram sacrificados 41 animais no país, em surtos de scrapie(11. Desde 2008, o diagnóstico de scrapie é realizado por meio da técnica de IHQ a partir de amostras do SNC e tecidos linfoides(12. Porém, no caso de tecidos linfoides associados à mucosa retal, pode haver necessidade de novas colheitas em curtos intervalos de tempo devido à escassez de tecido para o diagnóstico da doença que, segundo Leal et al.(13, deve ser de no mínimo três folículos linfoides (FL por amostra. Visando ao reconhecimento de boas técnicas para o monitoramento e o diagnóstico ante mortem da scrapie, o presente estudo teve por objetivo avaliar a quantidade de tecido linfoide associado à mucosa retal obtido pela técnica de biopsia retal e com vistas à avaliação imuno-histoquímica, bem como a possibilidade de se realizarem dois procedimentos de biopsia consecutivos, em diferentes intervalos de tempo, em ovinos e caprinos.

  19. Differentiation of hepatocytes from induced pluripotent stem cells derived from human hair follicle mesenchymal stem cells.

    Science.gov (United States)

    Shi, Xu; Lv, Shuang; He, Xia; Liu, Xiaomei; Sun, Meiyu; Li, Meiying; Chi, Guangfan; Li, Yulin

    2016-10-01

    Due to the limitations of organ donors and immune rejection in severe liver diseases, stem cell-based therapy presents a promising application for tissue repair and regeneration. As a novel cell source, mesenchymal stem cells separated from human hair follicles (HF-MSCs) are convenient to obtain and have no age limit. To date, the differentiation of HF-MSCs into hepatocytes has not been reported. In this study, we explored whether HF-MSCs and HF-MSC-derived-induced pluripotent stem cells (HF-iPS) could differentiate into hepatocytes in vitro. Flow cytometry, Oil Red O stain and Alizarin Red stain were used to identify the characteristics of HF-MSCs. The expression of liver-specific gene was detected by immunofluorescence and Quantitative Polymerase Chain Reaction. Periodic Acid-Schiff stain, Indocyanine Green stain and Low-Density Lipoprotein stain were performed to evaluate the functions of induced hepatocyte-like cells (HLCs). HF-MSCs were unable to differentiate into HLCs using previously reported procedures for MSCs from other tissues. However, HF-iPS efficiently induced the generation of HLCs that expressed hepatocyte markers and drug metabolism-related genes. HF-iPS can be used as novel and alternative cellular tools for inducing hepatocytes in vitro, simultaneously benefiting from utilizing HF-MSCs as a noninvasive and convenient cell source for reprogramming.

  20. B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis

    NARCIS (Netherlands)

    Cantaert, Tineke; Kolln, Johanna; Timmer, Trieneke; van der Pouw Kraan, Tineke C.; Vandooren, Bernard; Thurlings, Rogier M.; Cañete, Juan D.; Catrina, Anca I.; Out, Theo; Verweij, Cor L.; Zhang, Yiping; Tak, Paul P.; Baeten, Dominique

    2008-01-01

    B lymphocyte autoimmunity plays a crucial role in the pathogenesis of rheumatoid arthritis. The local production of autoantibodies and the presence of ectopic lymphoid neogenesis in the rheumatoid synovium suggest that these dedicated microenvironments resembling canonical lymphoid follicles may

  1. Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage.

    Science.gov (United States)

    Arck, Petra Clara; Overall, Rupert; Spatz, Katharina; Liezman, Christiane; Handjiski, Bori; Klapp, Burghard F; Birch-Machin, Mark A; Peters, Eva Milena Johanne

    2006-07-01

    Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.

  2. Effect of Glucocorticoid-Induced Insulin Resistance on Follicle Development and Ovulation1

    Science.gov (United States)

    Hackbart, Katherine S.; Cunha, Pauline M.; Meyer, Rudelle K.; Wiltbank, Milo C.

    2013-01-01

    ABSTRACT Polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenemia, polycystic ovaries, and menstrual disturbance and a clear association with insulin resistance. This research evaluated whether induction of insulin resistance, using dexamethasone (DEX), in a monovular animal model, the cow, could produce an ovarian phenotype similar to PCOS. In all of these experiments, DEX induced insulin resistance in cows as shown by increased glucose, insulin, and HOMA-IR (homeostasis model assessment of insulin resistance). Experiment 1: DEX induced anovulation (zero of five DEX vs. four of four control cows ovulated) and decreased circulating estradiol (E2). Experiment 2: Gonadotropin-releasing hormone (GnRH) was administered to determine pituitary and follicular responses during insulin resistance. GnRH induced a luteinizing hormone (LH) surge and ovulation in both DEX (seven of seven) and control (seven of seven) cows. Experiment 3: E2 was administered to determine hypothalamic responsiveness after induction of an E2 surge in DEX (eight of eight) and control (eight of eight) cows. An LH surge was induced in control (eight of eight) but not DEX (zero of eight) cows. All control (eight of eight) but only two of eight DEX cows ovulated within 60 h of E2 administration. Experiment 4: Short-term DEX was initiated 24 h after induced luteal regression to determine if DEX could acutely block ovulation before peak insulin resistance was induced, similar to progesterone (P4). All control (five of five), no P4-treated (zero of six), and 50% of DEX-treated (three of six) cows ovulated by 96 h after luteal regression. All anovular cows had reduced circulating E2. These data are consistent with DEX creating a lesion in hypothalamic positive feedback to E2 without altering pituitary responsiveness to GnRH or ovulatory responsiveness of follicles to LH. It remains to be determined if the considerable insulin resistance and the reduced follicular E2 production induced by DEX

  3. Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin.

    Directory of Open Access Journals (Sweden)

    Stephanie Morgan

    Full Text Available Chemotherapy treatment in premenopausal women has been linked to ovarian follicle loss and premature ovarian failure; the exact mechanism by which this occurs is uncertain. Here, two commonly used chemotherapeutic agents (cisplatin and doxorubicin were added to a mouse ovary culture system, to compare the sequence of events that leads to germ cell loss. The ability of imatinib mesylate to protect the ovary against cisplatin or doxorubicin-induced ovarian damage was also examined.Newborn mouse ovaries were cultured for a total of six days, exposed to a chemotherapeutic agent on the second day: this allowed for the examination of the earliest stages of follicle development. Cleaved PARP and TUNEL were used to assess apoptosis following drug treatment. Imatinib was added to cultures with cisplatin and doxorubicin to determine any protective effect.Histological analysis of ovaries treated with cisplatin showed oocyte-specific damage; in comparison doxorubicin preferentially caused damage to the granulosa cells. Cleaved PARP expression significantly increased for cisplatin (16 fold, p<0.001 and doxorubicin (3 fold, p<0.01. TUNEL staining gave little evidence of primordial follicle damage with either drug. Imatinib had a significant protective effect against cisplatin-induced follicle damage (p<0.01 but not against doxorubicin treatment.Cisplatin and doxorubicin both induced ovarian damage, but in a markedly different pattern, with imatinib protecting the ovary against damage by cisplatin but not doxorubicin. Any treatment designed to block the effects of chemotherapeutic agents on the ovary may need to be specific to the drug(s the patient is exposed to.

  4. Development and function of secondary and tertiary lymphoid organs in the small intestine and the colon

    Directory of Open Access Journals (Sweden)

    Manuela Buettner

    2016-09-01

    Full Text Available The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP in the small intestine and their colonic counterparts that develop in a programmed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT. In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP to large, mature isolated lymphoid follicles (ILF. Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi cells and the requirement for lymphotoxin beta (LTβ receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO. While so far it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation.

  5. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon

    Science.gov (United States)

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation. PMID

  6. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon.

    Science.gov (United States)

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer's patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation.

  7. Wnt5a attenuates Wnt3a-induced alkaline phosphatase expression in dental follicle cells

    International Nuclear Information System (INIS)

    Sakisaka, Yukihiko; Tsuchiya, Masahiro; Nakamura, Takashi; Tamura, Masato; Shimauchi, Hidetoshi; Nemoto, Eiji

    2015-01-01

    Wnt signaling regulates multiple cellular events such as cell proliferation, differentiation, and apoptosis through β-catenin-dependent canonical and β-catenin-independent noncanonical pathways. Canonical Wnt/β-catenin signaling can promote the differentiation of dental follicle cells, putative progenitor cells for cementoblasts, osteoblasts, and periodontal ligament cells, toward a cementoblast/osteoblast phenotype during root formation, but little is known about the biological significance of noncanonical Wnt signaling in this process. We identified the expression of Wnt5a, a representative noncanonical Wnt ligand, in tooth root lining cells (i.e. precementoblasts/cementoblasts) and dental follicle cells during mouse tooth root development, as assessed by immunohistochemistry. Silencing expression of the Wnt5a gene in a dental follicle cell line resulted in enhancement of the Wnt3a (a representative canonical Wnt ligand)-mediated increase in alkaline phosphatase (ALP) expression. Conversely, treatment with recombinant Wnt5a inhibited the increase in ALP expression, suggesting that Wnt5a signaling functions as a negative regulator of canonical Wnt-mediated ALP expression of dental follicle cells. Wnt5a did not affect the nuclear translocation of β-catenin as well as β-catenin-mediated transcriptional activation of T-cell factor (Tcf) triggered by Wnt3a, suggesting that Wnt5a inhibits the downstream part of the β-catenin-Tcf pathway. These findings suggest the existence of a feedback mechanism between canonical and noncanonical Wnt signaling during the differentiation of dental follicle cells. - Highlights: • Dental follicle cells express Wnt5a during tooth root development. • Silencing of Wnt5a enhances Wnt3a-mediated ALP expression of dental follicle cells. • Conversely, treatment with rWnt5a inhibited the increase in ALP expression. • Wnt5a functions as a negative regulator of Wnt3a-mediated ALP expression

  8. Wnt5a attenuates Wnt3a-induced alkaline phosphatase expression in dental follicle cells

    Energy Technology Data Exchange (ETDEWEB)

    Sakisaka, Yukihiko [Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Tsuchiya, Masahiro [Department of Oral Diagnosis, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Tohoku Fukushi University, Sendai 989-3201 (Japan); Nakamura, Takashi [Department of Pediatric Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Liason Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Tamura, Masato [Department of Biochemistry and Molecular Biology, Hokkaido University Graduate School of Dentistry, Sapporo 060-8586 (Japan); Shimauchi, Hidetoshi [Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Nemoto, Eiji, E-mail: e-nemoto@dent.tohoku.ac.jp [Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)

    2015-08-01

    Wnt signaling regulates multiple cellular events such as cell proliferation, differentiation, and apoptosis through β-catenin-dependent canonical and β-catenin-independent noncanonical pathways. Canonical Wnt/β-catenin signaling can promote the differentiation of dental follicle cells, putative progenitor cells for cementoblasts, osteoblasts, and periodontal ligament cells, toward a cementoblast/osteoblast phenotype during root formation, but little is known about the biological significance of noncanonical Wnt signaling in this process. We identified the expression of Wnt5a, a representative noncanonical Wnt ligand, in tooth root lining cells (i.e. precementoblasts/cementoblasts) and dental follicle cells during mouse tooth root development, as assessed by immunohistochemistry. Silencing expression of the Wnt5a gene in a dental follicle cell line resulted in enhancement of the Wnt3a (a representative canonical Wnt ligand)-mediated increase in alkaline phosphatase (ALP) expression. Conversely, treatment with recombinant Wnt5a inhibited the increase in ALP expression, suggesting that Wnt5a signaling functions as a negative regulator of canonical Wnt-mediated ALP expression of dental follicle cells. Wnt5a did not affect the nuclear translocation of β-catenin as well as β-catenin-mediated transcriptional activation of T-cell factor (Tcf) triggered by Wnt3a, suggesting that Wnt5a inhibits the downstream part of the β-catenin-Tcf pathway. These findings suggest the existence of a feedback mechanism between canonical and noncanonical Wnt signaling during the differentiation of dental follicle cells. - Highlights: • Dental follicle cells express Wnt5a during tooth root development. • Silencing of Wnt5a enhances Wnt3a-mediated ALP expression of dental follicle cells. • Conversely, treatment with rWnt5a inhibited the increase in ALP expression. • Wnt5a functions as a negative regulator of Wnt3a-mediated ALP expression.

  9. Pairing experimentation and computational modelling to understand the role of tissue inducer cells in the development of lymphoid organs

    Directory of Open Access Journals (Sweden)

    Kieran eAlden

    2012-07-01

    Full Text Available The use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insights into the role of tissue inducer cells and associated signalling pathways in the formation and function of lymphoid organs. Despite advances in experimental technologies, the molecular and cellular process orchestrating the formation of a complex 3-dimensional tissue is difficult to dissect using current approaches. Therefore, a robust set of simulation tools have been developed to model the processes involved in lymphoid tissue development. Specifically the role of different tissue inducer cell populations in the dynamic formation of Peyer's Patches has been examined. Utilising approaches from critical systems engineering an unbiased model of lymphoid tissue inducer cell function has been developed, that permits the development of emerging behaviours that are statistically not different from that observed in vivo. These results provide the confidence to utilise statistical methods to explore how the simulator predicts cellular behaviour and outcomes under different physiological conditions. Such methods, known as sensitivity analysis techniques, can provide insight into when a component part of the system (such as a particular cell type, adhesion molecule, or chemokine begins to have an influence on observed behaviour, and quantifies the effect a component part has on the end result: the formation of lymphoid tissue. Through use of such a principled approach in the design, calibration, and analysis of a computer simulation, a robust in silico tool can be developed which can both further the understanding of a biological system being explored, and act as a tool for the generation of hypotheses which can be tested utilising experimental approaches.

  10. Total lymphoid irradiation

    International Nuclear Information System (INIS)

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-01-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen

  11. Functional clonal deletion versus active suppression in transplantation tolerance induced by total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Morecki, S.; Leshem, B.; Weigensberg, M.; Bar, S.; Slavin, S.

    1985-01-01

    Transplantation tolerance and stable chimerism were established in adult mice conditioned with a short course of total-lymphoid irradiation (TLI) followed by infusion of 30 X 10(6) allogeneic bone marrow cells. Spleen cells of tolerant mice could not exert a proliferative or cytotoxic response against host-type cells in vitro and were unable to induce graft-versus-host reaction in secondary host-type recipients. The degree of suppression assessed by coculturing tolerant splenocytes in vitro in the one-way mixed lymphocyte reaction was quite variable--and, in some cases, was not at all demonstrable, although tolerance was clearly maintained. Suppression, when apparent, could not be ascribed to T lymphocytes. Suppressor cells were found to bind soybean agglutinin and could be separated from the nonsuppressive cells by means of this lectin. Dissociation of the suppressive population (SBA+ cells) from that which is normally alloreactive (SBA- cells) resulted in a suppressor cell-depleted fraction that was still unable to respond to host-type cells but regained reactivity to unrelated cells. Limiting dilution analysis of chimeric splenocytes revealed markedly reduced frequencies of cytotoxic T lymphocyte precursors (CTL-P) directed against host-type cells, as compared with normal splenocytes reacting against the same target cells. This difference was accentuated when these cells were sensitized to host-type target cells prior to plating in limiting dilution cultures. In 1:1 mixing experiments of normal and chimeric splenocytes, there was no evidence of any in vitro suppressive activity to account for hyporeactivity of chimeric cells against host-type cells. Thus, maintenance of TLI-induced tolerance seemed not to be mediated primarily through an active suppressor cell mechanism

  12. Innate lymphoid cells in secondary lymphoid organs.

    Science.gov (United States)

    Bar-Ephraïm, Yotam E; Mebius, Reina E

    2016-05-01

    The family of innate lymphoid cells (ILCs) has attracted attention in recent years as its members are important regulators of immunity, while they can also cause pathology. In both mouse and man, ILCs were initially discovered in developing lymph nodes as lymphoid tissue inducer (LTi) cells. These cells form the prototypic members of the ILC family and play a central role in the formation of secondary lymphoid organs (SLOs). In the absence of LTi cells, lymph nodes (LN) and Peyer's Patches (PP) fail to form in mice, although the splenic white pulp can develop normally. Besides LTi cells, the ILC family encompasses helper-like ILCs with functional distinctions as seen by T-helper cells, as well as cytotoxic natural killer (NK) cells. ILCs are still present in adult SLOs where they have been shown to play a role in lymphoid tissue regeneration. Furthermore, ILCs were implicated to interact with adaptive lymphocytes and influence the adaptive immune response. Here, we review the recent literature on the role of ILCs in secondary lymphoid tissue from the formation of SLOs to mature SLOs in adults, during homeostasis and pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Albumin infusion after reperfusion prevents gut ischemia-reperfusion-induced gut-associated lymphoid tissue atrophy.

    Science.gov (United States)

    Ikezawa, Fumie; Fukatsu, Kazuhiko; Moriya, Tomoyuki; Maeshima, Yoshinori; Okamoto, Koichi; Hara, Etsuko; Hiraide, Hoshio; Compher, Charlene W

    2006-01-01

    Our recent study clarified that gut ischemia-reperfusion (I/R) causes gut-associated lymphoid tissue (GALT) mass atrophy, a possible mechanism for increased morbidity of infectious complications after severe surgical insults. Because albumin administration reportedly reduces hemorrhagic shock-induced lung injury, we hypothesized that albumin treatment prevents GALT atrophy due to gut I/R. Male mice (n = 37) were randomized to albumin, normal saline, and sham groups. All groups underwent jugular vein catheter insertion. The albumin and normal saline groups underwent 75-minute occlusion of the superior mesenteric artery. During gut ischemia, all mice received normal saline infusions at 1.0 mL/h. The albumin group was given 5% bovine serum albumin in normal saline at 1.0 mL/h for 60 minutes after reperfusion, whereas the normal saline group received 0.9% sodium chloride at 1.0 mL/h. The sham group underwent laparotomy only. Mice were killed on day 1 or 7, and the entire small intestine was harvested. GALT lymphocytes were isolated and counted. Their phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, B220) were determined by flow cytometry. On day 1, the gut I/R groups showed significantly lower total lymphocyte and B cell numbers in Peyer's patches and the lamina propria than the sham group. However, the albumin infusion partially but significantly restored these cell numbers. On day 7, there were no significant differences in any of the parameters measured among the 3 groups. Albumin infusion after a gut ischemic insult may maintain gut immunity by preventing GALT atrophy.

  14. Fluorine-induced apoptosis and lipid peroxidation in human hair follicles in vitro.

    Science.gov (United States)

    Wang, Zheng-hui; Li, Xiao-li; Yang, Zhuang-qun; Xu, Min

    2010-12-01

    Fluoride is an essential trace element for human body; however, exposure to high amounts of fluoride has been documented to be correlated with an increasing risk of hair loss. To date, little is known about the mechanism(s) of how fluoride affects hair follicles. Here, we demonstrated that middle (1.0 mmol/L) and high (10.0 mmol/L) concentrations of sodium fluoride (NaF) significantly inhibited hair follicle elongation in vitro, but low NaF (0.1 mmol/L) showed little influence. Moreover, treatment with high levels of NaF resulted in a marked increase in terminal dUTP nick end labeling-positive cells in the outer layer of the outer root sheath, the dermal sheath, and the lower bulb matrix surrounding dermal papilla. Furthermore, the enhanced apoptosis was coupled with an increased oxidative stress manifested as higher malondialdehyde content. Additionally, the presence of selenium considerably antagonized the effects of middle NaF on hair follicles, with regard to either the suppression of hair growth or the induction of oxidative stress and apoptosis. In conclusion, exposure to high levels of fluoride compromises hair follicle growth and accelerate cell apoptosis in vitro. The toxicity of fluoride can be reduced by selenium, at least partially via the suppression of intracellular oxidative stress.

  15. VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK

    International Nuclear Information System (INIS)

    Li, Wei; Man, Xiao-Yong; Li, Chun-Ming; Chen, Jia-Qi; Zhou, Jiong; Cai, Sui-Qing; Lu, Zhong-Fa; Zheng, Min

    2012-01-01

    Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF 165 stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF 165 -induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF 165 . Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. -- Highlights: ► We examine the expression of VEGFR-2 on cultured human dermal papilla (DP) cells. ► VEGF 165 stimulated proliferation of human DP cells in a dose-dependent manner. ► This stimulation was through VEGFR-2-mediated activation of ERK.

  16. On the physics of laser-induced selective photothermolysis of hair follicles: Influence of wavelength, pulse duration, and epidermal cooling.

    Science.gov (United States)

    Svaasand, Lars O; Nelson, J Stuart

    2004-01-01

    The physical basis for optimization of wavelength, pulse duration, and cooling for laser-induced selective photothermolysis of hair follicles in human skin is discussed. The results indicate that the most important optimization parameter is the cooling efficiency of the technique utilized for epidermal protection. The optical penetration is approximately the same for lasers at 694, 755, and 800 nm. The penetration of radiation from Nd:yttrium-aluminum-garnet lasers at 1064 nm is, however, somewhat larger. Photothermal damage to the follicle is shown to be almost independent of laser pulse duration up to 100 ms. The results reveal that epidermal cooling by a 30-80-ms-long cryogen spurt immediately before laser exposure is the only efficient technique for laser pulse durations less than 10 ms. For longer pulse durations in the 30-100 ms range, protection can be done efficiently by skin cooling during laser exposure. For laser pulses of 100 ms, an extended precooling period, e.g., by bringing a cold object into good thermal contact with the skin for about 1 s, can be of value. Thermal quenching of laser induced epidermal temperature rise after pulsed exposure can most efficiently be done with a 20 ms cryogen spurt applied immediately after irradiation. (c) 2004 Society of Photo-Optical Instrumentation Engineers.

  17. Increased T-regulatory cells within lymphocyte follicles in moderate COPD

    DEFF Research Database (Denmark)

    Plumb, J; Smyth, L J C; Adams, H R

    2009-01-01

    Lymphoid follicles in the lung parenchyma are a characteristic feature of chronic obstructive pulmonary disease (COPD). There are reports of altered CD4 T-regulatory cell numbers in COPD lungs, but the location of these cells within COPD lung tissue specific follicles has not been investigated......, as well as lymphoid clusters lacking organisation. The percentage of CD4 cells that were T-regulatory cells were significantly increased (p = 0.02) within COPD (16%) follicles compared with smokers (10%) and nonsmokers (8%). In contrast, there was no change (p>0.05) in the percentage of T-regulatory cells...... in clusters or the subepithelium between groups. Lymphoid follicles in COPD patients have increased T-regulatory cells. Therefore, T-regulatory activity may be altered within COPD lymphoid follicles....

  18. Modulation of cisplatin-induced reactive oxygen species production by fullerene C(60 in normal and transformed lymphoid cells

    Directory of Open Access Journals (Sweden)

    D. V. Franskevych

    2016-02-01

    Full Text Available The early response of normal (Wistar rat thymocytes and transformed (mice lymphoid leukemia L1210 cells to treatment with anticancer drug cisplatin or to combined treatment with cisplatin and carbon nanostructure fullerene C60 was studied. We demonstrated with fluorescent probes DCFH-DA and TMRE that cisplatin at concentration 1 μg/ml induced reactive oxygen species (ROS production and decreased the value of mitochondrial membrane potential in both cell types. The combined treatment with cisplatin (1 μg/ml and fullerene C60 (7.2 μg/ml was shown to be followed by oppositely directed modulation of ROS production in thymocytes and L1210 cells. Cisplatin-induced ROS production was intensified in L1210 cells, while in thymocytes it was decreased. It is supposed that the different effects of combined treatment are associated with peculiarities of fullerene C60 accumulation and localization in normal and cancer cells.

  19. Circulating blocking factors of lymphoid-cell cytotoxicity in x-ray-induced rat small-bowel adenocarcinoma

    International Nuclear Information System (INIS)

    Stevens, R.H.; Brooks, G.P.; Osborne, J.W.

    1979-01-01

    Circulating blocking factors capable of abrogating cell-mediated immune responses measured by in vitro lymphoid-cell cytotoxicity were identified in the sera of Holtzman outbred rats 6 to 9 months after a single exposure of only the temporarily exteriorized, hypoxic ileum and jejunum to 1700 to 2000 R of X radiation. Such factors were found to exist in the serum of every animal exposed to the ionizing radiation regardless of whether a visibly identifiable small-bowel adenocarcinoma existed or subsequently would develop. Protection of cultured x-ray-induced rat small-bowel cancer cells from destruction by tumor-sensitized lymphoid cells as measured by the release of lactoperoxidase-catalyzed radioiodinated membrane proteins from the tumor target cells was conferred by the action of the blocking factors at both effector and target cell levels. The results of this study demonstrate that exposure of only the rat small intestine to ionizing radiation leads to elaboration of circulating factors identifiable several months postirradiation which will block cell-mediated immune responses directed against cancer cells developing in the exposed tissue

  20. The Innate Lymphoid Cell Precursor.

    Science.gov (United States)

    Ishizuka, Isabel E; Constantinides, Michael G; Gudjonson, Herman; Bendelac, Albert

    2016-05-20

    The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells. We also review the rapidly growing understanding of the network of transcription factors that direct the development of these lineages.

  1. Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice.

    Science.gov (United States)

    Montaldo, Elisa; Juelke, Kerstin; Romagnani, Chiara

    2015-08-01

    Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are "killer" ILCs, comprising NK cells, and "helper-like" ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL-22 and IL-17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell-to-cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases.

    Science.gov (United States)

    Mastropasqua, Rodolfo; Agnifili, Luca; Fasanella, Vincenzo; Nubile, Mario; Gnama, Agbeanda A; Falconio, Gennaro; Perri, Paolo; Di Staso, Silvio; Mariotti, Cesare

    2017-08-01

    Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.

  3. Nonselective inhibition of the epigenetic transcriptional regulator BET induces marked lymphoid and hematopoietic toxicity in mice

    International Nuclear Information System (INIS)

    Lee, Dong U.; Katavolos, Paula; Palanisamy, Gopinath; Katewa, Arna; Sioson, Charly; Corpuz, Janice; Pang, Jodie; DeMent, Kevin; Choo, Edna; Ghilardi, Nico; Diaz, Dolores; Danilenko, Dimitry M.

    2016-01-01

    Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4 and BRDT) are epigenetic transcriptional regulators required for efficient expression of growth promoting, cell cycle progression and antiapoptotic genes. Through their bromodomain, these proteins bind to acetylated lysine residues of histones and are recruited to transcriptionally active chromatin. Inhibition of the BET-histone interaction provides a tractable therapeutic strategy to treat diseases that may have epigenetic dysregulation. JQ1 is a small molecule that blocks BET interaction with histones. It has been shown to decrease proliferation of patient-derived multiple myeloma in vitro and to decrease tumor burden in vivo in xenograft mouse models. While targeting BET appears to be a viable and efficacious approach, the nonclinical safety profile of BET inhibition remains to be well-defined. We report that mice dosed with JQ1 at efficacious exposures demonstrate dose-dependent decreases in their lymphoid and immune cell compartments. At higher doses, JQ1 was not tolerated and due to induction of significant body weight loss led to early euthanasia. Flow cytometry analysis of lymphoid tissues showed a decrease in both B- and T-lymphocytes with a concomitant decrease in peripheral white blood cells that was confirmed by hematology. Further investigation with the inactive enantiomer of JQ1 showed that these in vivo effects were on-target mediated and not elicited through secondary pharmacology due to chemical structure.

  4. Nonselective inhibition of the epigenetic transcriptional regulator BET induces marked lymphoid and hematopoietic toxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong U., E-mail: lee.dong@gene.com [Department of Safety Assessment, Genentech, Inc., South San Francisco, CA 94080 (United States); Katavolos, Paula; Palanisamy, Gopinath [Department of Safety Assessment, Genentech, Inc., South San Francisco, CA 94080 (United States); Katewa, Arna [Department of Research Immunology, Genentech, Inc., South San Francisco, CA 94080 (United States); Sioson, Charly; Corpuz, Janice [Department of Safety Assessment, Genentech, Inc., South San Francisco, CA 94080 (United States); Pang, Jodie; DeMent, Kevin; Choo, Edna [Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, CA 94080 (United States); Ghilardi, Nico [Department of Research Immunology, Genentech, Inc., South San Francisco, CA 94080 (United States); Diaz, Dolores; Danilenko, Dimitry M. [Department of Safety Assessment, Genentech, Inc., South San Francisco, CA 94080 (United States)

    2016-06-01

    Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4 and BRDT) are epigenetic transcriptional regulators required for efficient expression of growth promoting, cell cycle progression and antiapoptotic genes. Through their bromodomain, these proteins bind to acetylated lysine residues of histones and are recruited to transcriptionally active chromatin. Inhibition of the BET-histone interaction provides a tractable therapeutic strategy to treat diseases that may have epigenetic dysregulation. JQ1 is a small molecule that blocks BET interaction with histones. It has been shown to decrease proliferation of patient-derived multiple myeloma in vitro and to decrease tumor burden in vivo in xenograft mouse models. While targeting BET appears to be a viable and efficacious approach, the nonclinical safety profile of BET inhibition remains to be well-defined. We report that mice dosed with JQ1 at efficacious exposures demonstrate dose-dependent decreases in their lymphoid and immune cell compartments. At higher doses, JQ1 was not tolerated and due to induction of significant body weight loss led to early euthanasia. Flow cytometry analysis of lymphoid tissues showed a decrease in both B- and T-lymphocytes with a concomitant decrease in peripheral white blood cells that was confirmed by hematology. Further investigation with the inactive enantiomer of JQ1 showed that these in vivo effects were on-target mediated and not elicited through secondary pharmacology due to chemical structure.

  5. IgA class switch occurs in the organized nasopharynx- and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut.

    Science.gov (United States)

    Shikina, Takashi; Hiroi, Takachika; Iwatani, Kohichi; Jang, Myoung Ho; Fukuyama, Satoshi; Tamura, Manabu; Kubo, Takeshi; Ishikawa, Hiromichi; Kiyono, Hiroshi

    2004-05-15

    Secretory IgA plays a crucial role in the host immune response as a first line of defense. A recent demonstration of in situ IgA class switching in intestinal lamina propria provided an opportunity to reconsider the model for the homing of IgA-committed B cells characterized by distinctive trafficking patterns to effector sites. Those effector sites depend on the organized mucosa-associated lymphoid tissues as their site of induction. In this report we show the preferential presence of IgM(+)B220(+) and IgA(+)B220(+) cells belonging to pre- and post-IgA isotype class-switched cells in the organized mucosa-associated lymphoid tissues, such as nasopharynx-associated lymphoid tissues, isolated lymphoid follicles, and Peyer's patches, and the defect of those populations in the diffuse effector tissues, such as the nasal passage and intestinal lamina propria. Consistent with these findings, the expressions of a series of IgA isotype class switch recombination-related molecules, including activation-induced cytidine deaminase, Ialpha-C micro circle transcripts, and Ialpha-C micro circle transcripts, were selectively detected in these organized mucosa-associated lymphoid structures, but not in the diffuse mucosal effector sites. Taken together, these findings suggest that IgA isotype class switching occurs only in the organized mucosa-associated lymphoid organs (e.g., nasopharynx-associated lymphoid tissues, isolated lymphoid follicles, and Peyer's patches), but not in the diffuse effector tissues of the upper respiratory and gastrointestinal tracts.

  6. Changes in homologous and heterologous gap junction contacts during maturation-inducing hormone-dependent meiotic resumption in ovarian follicles of Atlantic croaker

    Science.gov (United States)

    Bolamba, D.; Patino, R.; Yoshizaki, G.; Thomas, P.

    2003-01-01

    Homologous (granulosa cell-granulosa cell) gap junction (GJ) contacts increase in ovarian follicles of Atlantic croaker (Micropogonias undulatus) during the early (first) stage of maturation, but their profile during the second stage [i.e., during maturation-inducing hormone (MIH)-mediated meiotic resumption] is unknown. The profile of homologous GJ contacts during the second stage of maturation in croaker follicles was examined in this study and compared to that of heterologous (granulosa cell-oocyte) GJ, for which changes have been previously documented. Follicles were incubated with human chorionic gonadotropin to induce maturational competence (first stage), and then with MIH to induce meiotic resumption. The follicles were collected for examination immediately before and after different durations of MIH exposure until the oocyte had reached the stage of germinal vesicle breakdown (GVBD; index of meiotic resumption). Ultrathin sections were observed by transmission electron microscopy, and homologous and heterologous GJ contacts were quantified along a 100-??m segment of granulosa cell-zona radiata complex per follicle (three follicles/time/fish, n=3 fish). Relatively high numbers of both types of GJ were observed before and after the first few hours of MIH exposure (up to the stage of oil droplet coalescence). GJ numbers declined during partial yolk globule coalescence (at or near GVBD) and were just under 50% of starting values after the completion of GVBD (P<0.05). These results confirm earlier observations that GVBD temporally correlates with declining heterologous GJ contacts, and for the first time in teleosts show that there is a parallel decline in homologous GJ. The significance of the changes in homologous and heterologous GJ is uncertain and deserves further study. ?? 2003 Elsevier Science (USA). All rights reserved.

  7. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC(+) CD127(+) natural killer-like cells

    NARCIS (Netherlands)

    Cupedo, Tom; Crellin, Natasha K.; Papazian, Natalie; Rombouts, Elwin J.; Weijer, Kees; Grogan, Jane L.; Fibbe, Willem E.; Cornelissen, Jan J.; Spits, Hergen

    2009-01-01

    The human body contains over 500 individual lymph nodes, yet the biology of their formation is poorly understood. Here we identify human lymphoid tissue-inducer cells (LTi cells) as lineage-negative RORC(+) CD127(+) cells with the functional ability to interact with mesenchymal cells through

  8. Psoralen plus ultraviolet radiation-induced inhibition of DNA synthesis and viability in human lymphoid cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kraemer, K H; Waters, H L [National Cancer Inst., Bethesda, MD (USA); Ellingson, O L; Tarone, R E

    1979-08-01

    The present study investigated whether conditions of 8-methoxypsoralen (8-MOP) concentration and of exposure to high intensity long wavelength ultraviolet radiation (UV-A) during psoriasis and mycosis fungoides therapy might be sufficient to result directly in decreased lymphoid cell DNA synthesis and viability in vitro. Tritiated thymidine (/sup 3/HtdR) incorporation and cell growth following UV-A exposure alone or with 8-MOP was examined in peripheral blood lymphocytes and in Ebstein-Barr virus transformed human lymphoblastoid cell lines. UV-A exposure alone induced a dose-dependent inhibition of /sup 3/HTdR incorporation in both types of lymphoid cells. Pre-incubation with 0.1 ..mu..g/ml 8-MOP before UV-A exposure induced a significantly greater inhibition of /sup 3/HTdr incorporation. Further inhibition of /sup 3/HTdR incorporation was observed by preincubation of the lymphoblastoid cells with 1.0 ..mu..g/ml 8-MOP but not in the lymphocytes. The concentration of viable lymphoblastoid cells did not decrease below the original concentration after the highest dose of UV-A alone (29,00 J/m/sup 2/) but preincubation with 0.1 ..mu..g/ml 8-MOP resulted in 40% and 0.6% survival respectively after 3000 J/m/sup 2/. This study suggested that the low doses of 8-MOP and UV-A received by patients' lymphocytes may be sufficient to explain the decreased DNA synthesis found in their circulating leucocytes. (author).

  9. Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial

    Science.gov (United States)

    Bayram, Neriman; van Wely, Madelon; Kaaijk, Eugenie M; Bossuyt, Patrick M M; van der Veen, Fulco

    2004-01-01

    Objective To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome. Design Randomised controlled trial. Setting Secondary and tertiary hospitals in the Netherlands. Participants 168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone. Intervention Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone. Main outcome measure Ongoing pregnancy within 12 months. Results. The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86). Conclusion The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy. PMID:14739186

  10. Inducible tertiary lymphoid structures, autoimmunity, and exocrine dysfunction in a novel model of salivary gland inflammation in C57BL/6 mice.

    Science.gov (United States)

    Bombardieri, Michele; Barone, Francesca; Lucchesi, Davide; Nayar, Saba; van den Berg, Wim B; Proctor, Gordon; Buckley, Christopher D; Pitzalis, Costantino

    2012-10-01

    Salivary glands in patients with Sjögren's syndrome (SS) develop ectopic lymphoid structures (ELS) characterized by B/T cell compartmentalization, the formation of high endothelial venules, follicular dendritic cell networks, functional B cell activation with expression of activation-induced cytidine deaminase, as well as local differentiation of autoreactive plasma cells. The mechanisms that trigger ELS formation, autoimmunity, and exocrine dysfunction in SS are largely unknown. In this article, we present a novel model of inducible ectopic lymphoid tissue formation, breach of humoral self-tolerance, and salivary hypofunction after delivery of a replication-deficient adenovirus-5 in submandibular glands of C57BL/6 mice through retrograde excretory duct cannulation. In this model, inflammation rapidly and consistently evolves from diffuse infiltration toward the development of SS-like periductal lymphoid aggregates within 2 wk from AdV delivery. These infiltrates progressively acquire ELS features and support functional GL7(+)/activation-induced cytidine deaminase(+) germinal centers. Formation of ELS is preceded by ectopic expression of lymphoid chemokines CXCL13, CCL19, and lymphotoxin-β, and is associated with development of anti-nuclear Abs in up to 75% of mice. Finally, reduction in salivary flow was observed over 3 wk post-AdV infection, consistent with exocrine gland dysfunction as a consequence of the inflammatory response. This novel model has the potential to unravel the cellular and molecular mechanisms that regulate ELS formation and their role in exocrine dysfunction and autoimmunity in SS.

  11. Inducible tertiary lymphoid structures, autoimmunity and exocrine dysfunction in a novel model of salivary gland inflammation in C57BL/6 mice§

    Science.gov (United States)

    Bombardieri, Michele; Barone, Francesca; Lucchesi, Davide; Nayar, Saba; van den Berg, Wim B; Proctor, Gordon; Buckley, Christopher D; Pitzalis, Costantino

    2012-01-01

    Salivary glands in patients with Sjögren’s syndrome (SS) develop ectopic lymphoid structures (ELS) characterized by B/T cell compartmentalization, the formation of high endothelial venules (HEV), follicular dendritic cell networks (FDCs), functional B cell activation with expression of activation-induced cytidine deaminase (AID) as well as local differentiation of autoreactive plasma cells. The mechanisms triggering ELS formation, autoimmunity and exocrine dysfunction in SS are largely unknown. Here we present a novel model of inducible ectopic lymphoid tissue formation, breach of humoral self-tolerance and salivary hypofunction following delivery of a replication-deficient adenovirus-5 (AdV5) in submandibular glands of C57BL/6 mice through retrograde excretory duct cannulation. In this model, inflammation rapidly and consistently evolves from diffuse infiltration towards the development of SS-like periductal lymphoid aggregates within 2 weeks from AdV delivery. These infiltrates progressively acquire ELS features and support functional GL7+/AID+ germinal centers. Formation of ELS is preceded by ectopic expression of lymphoid chemokines CXCL13, CCL19 and lymphotoxin-β and is associated with development of anti-nuclear antibodies in up to 75% of mice. Finally, reduction in salivary flow was observed over 3 weeks post AdV infection consistent with exocrine gland dysfunction as a consequence of the inflammatory response. This novel model has the potential to unravel the cellular and molecular mechanisms regulating ELS formation and their role in exocrine dysfunction and autoimmunity in SS. PMID:22942425

  12. Dermal white adipose tissue undergoes major morphological changes during the spontaneous and induced murine hair follicle cycling: a reappraisal.

    Science.gov (United States)

    Foster, April R; Nicu, Carina; Schneider, Marlon R; Hinde, Eleanor; Paus, Ralf

    2018-07-01

    In murine skin, dermal white adipose tissue (DWAT) undergoes major changes in thickness in synchrony with the hair cycle (HC); however, the underlying mechanisms remain unclear. We sought to elucidate whether increased DWAT thickness during anagen is mediated by adipocyte hypertrophy or adipogenesis, and whether lipolysis or apoptosis can explain the decreased DWAT thickness during catagen. In addition, we compared HC-associated DWAT changes between spontaneous and depilation-induced hair follicle (HF) cycling to distinguish between spontaneous and HF trauma-induced events. We show that HC-dependent DWAT remodelling is not an artefact caused by fluctuations in HF down-growth, and that dermal adipocyte (DA) proliferation and hypertrophy are HC-dependent, while classical DA apoptosis is absent. However, none of these changes plausibly accounts for HC-dependent oscillations in DWAT thickness. Contrary to previous studies, in vivo BODIPY uptake suggests that increased DWAT thickness during anagen occurs via hypertrophy rather than hyperplasia. From immunohistomorphometry, DWAT thickness likely undergoes thinning during catagen by lipolysis. Hence, we postulate that progressive, lipogenesis-driven DA hypertrophy followed by dynamic switches between lipogenesis and lipolysis underlie DWAT fluctuations in the spontaneous HC, and dismiss apoptosis as a mechanism of DWAT reduction. Moreover, the depilation-induced HC displays increased DWAT thickness, area, and DA number, but decreased DA volume/area compared to the spontaneous HC. Thus, DWAT shows additional, novel HF wounding-related responses during the induced HC. This systematic reappraisal provides important pointers for subsequent functional and mechanistic studies, and introduces the depilation-induced murine HC as a model for dissecting HF-DWAT interactions under conditions of wounding/stress.

  13. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

    2011-12-28

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  14. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Federica Marchesi

    2011-12-01

    Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  15. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    International Nuclear Information System (INIS)

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21 + follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response

  16. Cell-mediated immune responses in the head-associated lymphoid tissues induced to a live attenuated avian coronavirus vaccine.

    Science.gov (United States)

    Gurjar, Rucha S; Gulley, Stephen L; van Ginkel, Frederik W

    2013-12-01

    Humoral immunity is important for controlling viral diseases of poultry, but recent studies have indicated that cytotoxic T cells also play an important role in the immune response to infectious bronchitis virus (IBV). To better understand the cell mediated immune responses to IBV in the mucosal and systemic immune compartments chickens were ocularly vaccinated with IBV. This induced a lymphocyte expansion in head-associated lymphoid tissues (HALT) and to a lesser extent in the spleen, followed by a rapid decline, probably due to homing of lymphocytes out of these organs and contraction of the lymphocyte population. This interpretation was supported by observations that changes in mononuclear cells were mirrored by that in CD3(+)CD44(+) T cell abundance, which presumably represent T effector cells. Increased interferon gamma (IFN-γ) expression was observed in the mucosal immune compartment, i.e., HALT, after primary vaccination, but shifted to the systemic immune compartment after boosting. In contrast, the expression of cytotoxicity-associated genes, i.e., granzyme A (GZMA) and perforin mRNA, remained associated with the HALT after boosting. Thus, an Ark-type IBV ocular vaccine induces a central memory IFN-γ response in the spleen while the cytotoxic effector memory response, as measured by GZMA and perforin mRNA expression, remains associated with CALT after boosting. Copyright © 2013. Published by Elsevier Ltd.

  17. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: a review.

    Science.gov (United States)

    Casteleyn, C; Doom, M; Lambrechts, E; Van den Broeck, W; Simoens, P; Cornillie, P

    2010-06-01

    The lymphoid tissue that is associated with the intestinal tract, the so-called gut-associated lymphoid tissue (GALT), is well developed in the chicken. Depending on the location, it is present as aggregations of lymphoid cells, or organized in lymphoid follicles and tonsils. From proximal to distal, the intestinal tract contains a pharyngeal tonsil, diffuse lymphoid tissue and lymphoid follicles in the cervical and thoracic parts of the oesophagus, an oesophageal tonsil, diffuse lymphoid tissue in the proventriculus, a pyloric tonsil, Peyer's patches, Meckel's diverticulum, two caecal tonsils, diffuse lymphoid tissue in the rectum, the bursa of Fabricius, and diffuse lymphoid tissue in the wall of the proctodeum. The lymphoid tissues are frequently covered by a lympho-epithelium that is infiltrated by lymphoid cells. Such an epithelium often contains M or microfold cells, which are specialized in antigen sampling and transport antigens to the underlying lymphoid tissue. A solid knowledge of the avian GALT could contribute to the development of vaccines to be administered orally. Additionally, immune stimulation via pre- and probiotics is based on the presence of a well-developed intestinal immune system.

  18. Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial

    NARCIS (Netherlands)

    Bayram, Neriman; van Wely, Madelon; Kaaijk, Eugenie M.; Bossuyt, Patrick M. M.; van der Veen, Fulco

    2004-01-01

    Objective To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with clomiphene resistant polycystic ovary syndrome. Design Randomised controlled trial. Setting Secondary and tertiary hospitals in the

  19. Transcriptome response to hormonal manipulation of follicle-enclosed oocytes in rainbow trout

    Science.gov (United States)

    Captive fish often display reproductive dysfunction associated with follicle maturation. Gonadotropins and the progestogen maturation-inducing hormones (MIH) are important regulators of follicle maturation; however, their actions including regulating follicle maturation are not fully understood. The...

  20. n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1.

    Directory of Open Access Journals (Sweden)

    Tsung-Hua Hsieh

    Full Text Available Environmental hormones play important roles in regulating the expression of genes involved in cell proliferation, drug resistance, and breast cancer risk; however, their precise role in human breast cancer cells during cancer progression remains unclear. To elucidate the effect of the most widely used industrial phthalate, n-butyl benzyl phthalate (BBP, on cancer progression, we evaluated the results of BBP treatment using a whole human genome cDNA microarray and MetaCore software and selected candidate genes whose expression was changed by more than ten-fold by BBP compared with controls to analyze the signaling pathways in human breast cancer initiating cells (R2d. A total of 473 genes were upregulated, and 468 were downregulated. Most of these genes are involved in proliferation, epithelial-mesenchymal transition, and angiogenesis signaling. BBP induced the viability, invasion and migration, and tube formation in vitro, and Matrigel plug angiogenesis in vivo of R2d and MCF-7. Furthermore, the viability and invasion and migration of these cell lines following BBP treatment was reduced by transfection with a small interfering RNA targeting the mRNA for lymphoid enhancer-binding factor 1; notably, the altered expression of this gene consistently differentiated tumors expressing genes involved in proliferation, epithelial-mesenchymal transition, and angiogenesis. These findings contribute to our understanding of the molecular impact of the environmental hormone BBP and suggest possible strategies for preventing and treating human breast cancer.

  1. Generation of Induced Pluripotent Stem Cells from Hair Follicle Bulge Neural Crest Stem Cells

    NARCIS (Netherlands)

    Ma, Ming-San; Czepiel, Marcin; Krause, Tina; Schaefer, Karl-Herbert; Boddeke, Erik; Copray, Sjef

    2014-01-01

    Induced pluripotent stem cells (iPSCs) are promising candidates for the study of disease models as well as for tissue engineering purposes. Part of a strategy to develop safe reprogramming technique is reducing the number of exogenous reprogramming factors. Some cells types are more prone to

  2. Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in Subjects with Asthma.

    Science.gov (United States)

    Chen, Ruchong; Smith, Steven G; Salter, Brittany; El-Gammal, Amani; Oliveria, John Paul; Obminski, Caitlin; Watson, Rick; O'Byrne, Paul M; Gauvreau, Gail M; Sehmi, Roma

    2017-09-15

    Group 2 innate lymphoid cells (ILC2), a major source of type 2 cytokines, initiate eosinophilic inflammatory responses in murine models of asthma. To investigate the role of ILC2 in allergen-induced airway eosinophilic responses in subjects with atopy and asthma. Using a diluent-controlled allergen challenge crossover study, where all subjects (n = 10) developed allergen-induced early and late responses, airway eosinophilia, and increased methacholine airway responsiveness, bone marrow, blood, and sputum samples were collected before and after inhalation challenge. ILC2 (lin - FcεRI - CD45 + CD127 + ST2 + ) and CD4 + T lymphocytes were enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression. Steroid sensitivity of ILC2 and CD4 + T cells was investigated in vitro. A significant increase in total, IL-5 + , IL-13 + , and CRTH2 + ILC2 was found in sputum, 24 hours after allergen, coincident with a significant decrease in blood ILC2. Total, IL-5 + , and IL-13 + , but not CRTH2 + , CD4 + T cells significantly increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow, only CD4 + cells demonstrated increased activation after allergen. Airway eosinophilia correlated with IL-5 + ILC2 at all time points and allergen-induced changes in IL-5 + CD4 + cells at 48 hours after allergen. Dexamethasone significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by both cell types. Innate and adaptive immune cells are increased in the airways associated with allergic asthmatic responses. Total and type 2 cytokine-positive ILC2 are increased only within the airways, whereas CD4 + T lymphocytes demonstrated local and systemic increases. Steroid sensitivity of both cells may explain effectiveness of this therapy in those with mild asthma.

  3. CD8 T cells primed in the gut-associated lymphoid tissue induce immune-mediated cholangitis in mice.

    Science.gov (United States)

    Seidel, Daniel; Eickmeier, Ira; Kühl, Anja A; Hamann, Alf; Loddenkemper, Christoph; Schott, Eckart

    2014-02-01

    The pathogenesis of primary sclerosing cholangitis (PSC) remains poorly understood. Since PSC predominantly occurs in patients with inflammatory bowel disease, autoimmunity triggered by activated T cells migrating from the gut to the liver is a possible mechanism. We hypothesized that T cells primed in the gut-associated lymphoid tissue (GALT) by a specific antigen migrate to the liver and cause cholangitis when they recognize the same antigen on cholangiocytes. We induced ovalbumin-dependent colitis in mice that express ovalbumin in biliary epithelia (ASBT-OVA mice) and crossed ASBT-OVA mice with mice that express ovalbumin in enterocytes (iFABP-OVA mice). We analyzed T-cell activation in the GALT and crossreactivity to the same antigen in the liver as well as the effects of colitis per se on antigen-presentation and T-cell activation in the liver. Intrarectal application of ovalbumin followed by transfer of CD8 OT-I T cells led to antigen-dependent colitis. CD8 T cells primed in the GALT acquired effector function and the capability to migrate to the liver, where they caused cholangitis in a strictly antigen-dependent manner. Likewise, cholangitis developed in mice expressing ovalbumin simultaneously in biliary epithelia and enterocytes after transfer of OT-I T cells. Dextran sodium sulfate colitis led to increased levels of inflammatory cytokines in the portal venous blood, induced activation of resident liver dendritic cells, and promoted the induction of T-cell-dependent cholangitis. Our data strengthen the notion that immune-mediated cholangitis is caused by T cells primed in the GALT and provide the first link between colitis and cholangitis in an antigen-dependent mouse model. © 2013 by the American Association for the Study of Liver Diseases.

  4. Transcriptional control of innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Bernink, Jochem; Peters, Charlotte; Spits, Hergen

    2012-01-01

    Cells that belong to the family of innate lymphoid cells (ILCs) not only form a first line of defense against invading microbes, but also play essential roles in tissue remodeling and immune pathology. Ror?t+ ILCs, producing the cytokines IL-22 and IL-17, include lymphoid tissue inducer (LTi) cells

  5. Epithelial-mesenchymal transition in keloid tissues and TGF-β1-induced hair follicle outer root sheath keratinocytes.

    Science.gov (United States)

    Yan, Li; Cao, Rui; Wang, Lianzhao; Liu, Yuanbo; Pan, Bo; Yin, Yanhua; Lv, Xiaoyan; Zhuang, Qiang; Sun, Xuejian; Xiao, Ran

    2015-01-01

    Keloid is a skin fibrotic disease with the characteristics of recurrence and invasion, its pathogenesis still remains unrevealed. The epithelial-mesenchymal transition (EMT) is critical for wound healing, fibrosis, recurrence, and invasion of cancer. We sought to investigate the EMT in keloid and the mechanism through which the EMT regulates keloid formation. In keloid tissues, the expressions of EMT-associated markers and transforming growth factor (TGF)-β1/Smad3 signaling were examined by immunohistochemistry. In the keloid epidermis and dermal tissue, the expressions of genes related to the regulation of skin homeostasis, fibroblast growth factor receptor 2 (FGFR2) and p63, were analyzed using quantitative real-time polymerase chain reaction. The results showed that accompanying the loss of the epithelial marker E-cadherin and the gain of the mesenchymal markers fibroblast-specific protein 1 (FSP1) and vimentin in epithelial cells from epidermis and skin appendages, and in endothelial cells from dermal microvessels, enhanced TGF-β1 expression and Smad3 phosphorylation were noted in keloid tissues. Moreover, alternative splicing of the FGFR2 gene switched the predominantly expressed isoform from FGFR2-IIIb to -IIIc, concomitant with the decreased expression of ΔNp63 and TAp63, which changes might partially account for abnormal epidermis and appendages in keloids. In addition, we found that TGF-β1-induced hair follicle outer root sheath keratinocytes (ORSKs) and normal skin epithelial cells underwent EMT in vitro with ORSKs exhibiting more obvious EMT changes and more similar expression profiles for EMT-associated and skin homeostasis-related genes as in keloid tissues, suggesting that ORSKs might play crucial roles in the EMT in keloids. Our study provided insights into the molecular mechanisms mediating the EMT pathogenesis of keloids. © 2015 by the Wound Healing Society.

  6. Increased expression of beta 2-microglobulin and histocompatibility antigens on human lymphoid cells induced by interferon

    DEFF Research Database (Denmark)

    Hokland, M; Heron, I; Berg, K

    1982-01-01

    Normal human peripheral blood lymphocytes were incubated in the presence of different concentrations of interferon for various incubation periods. Subsequently, the amount of beta 2-Microglobulin and HLA-A, B and C surface antigens was estimated by means of quantitative immunofluorescence (flow...... cytofluorometry) and by a radioimmunoassay for beta 2-Microglobulin. It was found that the amounts of these MHC antigens increased in a dose and time-dependent way after interferon treatment. Furthermore, the influence of different temperatures on this IFN-induced increase in beta 2-Microglobulin was gradually...

  7. Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells.

    Science.gov (United States)

    Komlósi, Zsolt I; Kovács, Nóra; van de Veen, Willem; Kirsch, Anna Isabella; Fahrner, Heinz Benedikt; Wawrzyniak, Marcin; Rebane, Ana; Stanic, Barbara; Palomares, Oscar; Rückert, Beate; Menz, Günter; Akdis, Mübeccel; Losonczy, György; Akdis, Cezmi A

    2017-09-20

    Type 3 innate lymphoid cells (ILC3s) are involved in maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified. We aimed to investigate the ILC3-B-cell interaction that probably takes place in human tonsils. ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmatic patients and healthy control subjects. A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15-activated CD40L + ILC3s helped B-cell survival, proliferation, and differentiation of IL-10-secreting, PD-L1-expressing functional itBreg cells in a CD40L- and B cell-activating factor receptor-dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatic patients. Human CD40L + ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. The mechanism of radiation-induced interphase death of lymphoid cells: A new hypothesis

    International Nuclear Information System (INIS)

    Eidus, L.K.; Korystov, Yu.N.; Dobrovinskaja, O.R.; Shaposhnikova, V.V.

    1990-01-01

    The interphase death of irradiated rat thymocytes depends on their concentration during postirradiation incubation. The kinetics of pycnosis and cell death determined with the trypan blue exclusion test in the samples with the highest cell concentration (1-2 x 10(7) cells/ml) is consistent with the data available in the literature, whereas the samples with the lowest concentration (2 x 10(5) cells/ml) undergo almost no pycnosis and death after irradiation with doses up to 50 Gy. On the basis of these results, we suggest a new mechanism of interphase death involving an interaction between irradiated thymocytes and the fraction of thymus cells possessing cytocidal activity. The observed correlation between the cytocidal activity and interphase death of thymocytes from animals of different ages favors our mechanism. It was found that the inhibitors which prevent the conjugation of killer cells and their targets do not influence interphase death, while the substances which block the secretion of cytotoxic factors or their action on the target membrane do protect from interphase death. Thus we suggest that the irradiation activates the killer cells to secrete some cytotoxic factors which induce pycnosis and interphase death of thymocytes

  9. STUDY ON EFFICACY OF DIATOMACEOUS EARTH TO AMELIORATE AFLATOXIN - INDUCED PATHO-MORPHOLOGICAL CHANGES IN LYMPHOID ORGANS OF BROILER CHICKEN

    Directory of Open Access Journals (Sweden)

    A.W. Lakkawar

    2017-12-01

    Full Text Available The efficacy of Diatomaceous earth (DAE in reducing the detrimental effects of aflatoxin (AF in broiler diet was evaluated. DAE was supplemented 2000 mg/kg of feed along with 0.5 and 1 ppm of AF in feed. A total of 240 healthy day old broiler chicks were divided into 6 groups comprising of control and treatment groups. Feeding of AF resulted in reduction in size of the thymus, spleen and bursa of Fabricius. In addition, petechial haemorrhages were observed on the surface of the thymus. Histopathology revealed varying degree of lymphocytolysis and depletion of lymphoid cells in thymus, spleen and bursa of Fabricius. In addition, the ceacal tonsils also revealed a mild to moderate degree of lymphoid depletion. The supplementation of DAE to aflatoxin-mixed feed revealed significant improvement characterised by decreased severity of lesions in lymphoid organs. The macroscopic and microscopic changes in the birds fed DAE in combination with AF included those that were observed in AF- alone fed birds, but of reduced magnitude and severity. The study concluded that 2% DAE in feed can be effectively used to reduce the the histotoxic effects of aflatoxin on lymphoid organs in broiler chicken.

  10. In vivo administration of interferon alpha and interleukin 2 induces proliferation of lymphoid cells in the organs of mice

    International Nuclear Information System (INIS)

    Puri, R.K.; Travis, W.D.; Rosenberg, S.A.

    1990-01-01

    We have previously shown that interleukin 2 (IL-2) synergizes with interferon alpha (IFN-alpha) in mediating the regression of established pulmonary and hepatic metastases and the reduction of intradermal tumor in various murine tumor models. To understand the mechanism of synergy, we have examined lymphoid cell proliferation in various organs of mice in response to IL-2 and IFN-alpha administration. We have utilized a technique for labeling newly synthesized DNA in vivo with 5-[125I]iodo-2'-deoxyuridine to examine proliferation of endogenous cells in response to IL-2 and IL-2 plus IFN-alpha. A proliferation index was calculated by dividing cpm in the tissues treated with cytokines by cpm obtained in corresponding tissues of control mice. After 4 days of IL-2 administration, a significant uptake of 5-[125I]iodo-2'-deoxyuridine was observed in the lungs, liver, kidneys, and spleen (proliferation index of 13, 10.3, 3.6, and 3.2, respectively). IFN-alpha alone mediated very little incorporation of radiolabel but when administered in combination with IL-2 a reduction of IL-2-induced proliferation was seen on day 4. For example 19,272 +/- 4,556 cpm (mean +/- SE) were obtained in the liver of IL-2-treated mice, compared to 8,103 +/- 2,111 cpm in livers of IL-2 plus IFN-alpha-treated mice (P less than 0.05). Similar inhibition of IL-2-induced proliferation was observed in the lungs, kidneys, and spleen. In contrast, on days 7 or 8, higher uptake of radiolabel was obtained in IFN-alpha plus IL-2-treated lungs, liver, and kidneys, compared to organs of mice treated with IL-2 alone or IFN-alpha alone. A proliferation index of 30.5, 9.8, and 10 was obtained in the lungs, liver, and kidneys of IL-2- plus IFN-alpha-treated animals, compared to 9.6, 3.6, and 5.5 in the corresponding organs of IL-2-treated mice

  11. Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27Kip1 promoter in primordial follicles.

    Science.gov (United States)

    Jang, Hoon; Na, Younghwa; Hong, Kwonho; Lee, Sangho; Moon, Sohyeon; Cho, Minha; Park, Miseon; Lee, Ok-Hee; Chang, Eun Mi; Lee, Dong Ryul; Ko, Jung Jae; Lee, Woo Sik; Choi, Youngsok

    2017-10-01

    Premature ovarian failure during chemotherapy is a serious problem for young women with cancer. To preserve the fertility of these patients, approaches to prevent chemotherapy-induced ovarian failure are needed. In a previous study, we reported that melatonin treatment prevents the depletion of the dormant follicle pool via repression of the simultaneous activation of dormant primordial follicles by cisplatin. However, melatonin's protective effect was only partial and thus insufficient. In this study, we found that the hormone ghrelin enhances the protective effect of melatonin against cisplatin-induced ovarian failure in mouse model. Co-administration of melatonin and ghrelin more effectively prevented cisplatin-induced follicle disruption. Simultaneous treatment with melatonin and ghrelin almost restored the number of primordial follicles and the corpus luteum in cisplatin-treated ovaries, compared with single administration. We found melatonin and ghrelin receptors on the cell membrane of premature oocytes of primordial follicles. In addition, melatonin and ghrelin co-administration inhibited the cisplatin-induced phosphorylation of PTEN and FOXO3a that induces cytoplasmic translocation of FOXO3a. Inhibition of FOXO3a phosphorylation by melatonin and ghrelin increased the binding affinity of FOXO3a for the p27 Kip1 promoter in primordial follicles. Co-administration of melatonin and ghrelin in cisplatin-treated ovaries restored the expression of p27 Kip1 , which is critical for retention of the dormant status of primordial follicles. In conclusion, these findings suggest that melatonin and ghrelin co-administration is suitable for use as a fertoprotective adjuvant therapy during cisplatin chemotherapy in young female cancer patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses.

    Science.gov (United States)

    De Grove, Katrien C; Provoost, Sharen; Hendriks, Rudi W; McKenzie, Andrew N J; Seys, Leen J M; Kumar, Smitha; Maes, Tania; Brusselle, Guy G; Joos, Guy F

    2017-01-01

    Although the prominent role of T H 2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can also contribute to orchestration of allergic responses. Several experimental and epidemiologic studies have provided evidence that allergen-induced airway responses can be further enhanced on exposure to environmental pollutants, such as diesel exhaust particles (DEPs). However, the components and pathways responsible remain incompletely known. We sought to investigate the relative contribution of ILC2 and adaptive T H 2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. Wild-type, Gata-3 +/nlslacZ (Gata-3-haploinsufficient), RAR-related orphan receptor α (RORα) fl/fl IL7R Cre (ILC2-deficient), and recombination-activating gene (Rag) 2 -/- mice were challenged with saline, DEPs, or house dust mite (HDM) or DEP+HDM. Airway hyperresponsiveness, as well as inflammation, and intracellular cytokine expression in ILC2s and T H 2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed. Concomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and T H 2 cells, type 2 cytokine production, and airway hyperresponsiveness compared with sole DEPs or HDM. Reduced Gata-3 expression decreased the number of functional ILC2s and T H 2 cells in DEP+HDM-exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, although the DEP-enhanced allergic inflammation was marginally reduced in ILC2-deficient mice that received combined DEP+HDM, it was abolished in DEP+HDM-exposed Rag2 -/- mice. These data indicate that dysregulation of ILC2s and T H 2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure. Copyright © 2016 American

  13. Morphological Studies on the Postnatal Development of the Gut-associated Lymphoid Tissues of the Rabbit Cecum

    Directory of Open Access Journals (Sweden)

    Abdelmohaimen M. Saleh

    2012-10-01

    Full Text Available The macroscopic, morphometric, light and scanning electron microscopic structure of gut-associated lymphoid tissue (GALT of cecum were studied in the rabbits aged from birth to 16 weeks. The GALT were formed of lymph follicles covered by low columnar epithelium containing intraepithelial lymphocytes and leukocytes. They were concentrated at the ileocecal entrance (ileocecal patch and in the blind end of the cecum vermiform appendix. In the ileocecal patch, GALT were in direct contact with the lumen, while those of the appendix were covered by the interval intestinal villi in young rabbits and mucosal folds in the adult rabbits. The lymphoid follicles of the ileocecal patch were composed of dome region and germinal center and were separated by narrow inter-follicular areas. Whereas, the lymphoid follicles of the appendix were composed dome region and germinal center in the newly born rabbits and up to the 2nd week of age, the follicles became composed of four different sites: dome region, germinal center, coronal area, and a wide interfollicular area between neighboring follicles. Morphometrically; the dimensions of the lymphoid follicles of the cecal GALT increased in size with the advancement of the age. By SEM the lymphoid structures covered with special epithelium consisted of two types of cell absorptive enterocytes and M cells. The M cells in the cecal patch were microvilliated and present on the tips and sides of the dome lymphoid regions while in the appendix were non-microvilliated and present only on the sides of the dome regions.

  14. Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

    International Nuclear Information System (INIS)

    Almaraz, R.

    1981-01-01

    The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth

  15. Induction of ovarian cystic follicles in sheep.

    Science.gov (United States)

    Christman, S A; Bailey, M T; Head, W A; Wheaton, J E

    2000-10-01

    Cystic follicles are a significant cause of infertility in women, dairy cattle and sheep. Sheep were used as a model to identify factors that may elicit formation of cystic follicles. Insulin resistance and elevated LH activity were tested in overweight ewes because of associations among these factors and the formation of cystic follicles. Sheep were synchronized using a progesterone-releasing pessary and insulin resistance was induced during the synchronization period through administration of bovine somatotropin. Following removal of pessaries follicular growth was stimulated by treatment with eCG or eCG and hCG (PG-600). Follicular growth was monitored via daily transrectal ultrasonography and blood samples were collected for hormonal analyses. Six of 18 ewes had a subnormal or absent preovulatory gonadotropin surge and developed cystic follicles. Neither insulin resistance nor elevated LH activity were associated with formation of cystic follicles. Ewes that developed cystic follicles were heavier (93 +/- 4 kg) than ewes that ovulated (81 +/- 3 kg; P = 0.02). Furthermore, following pessary removal and initiation of daily ultrasonography, ewes that developed cystic follicles lost body weight (-3 +/- 1%), while ovulatory ewes continued to gain body weight (1 +/- 1%; P = 0.005). It is speculated that in heavy ewes metabolic factors associated with acute body weight loss inhibit the positive feedback of estradiol and thereby suppress the preovulatory gonadotropin surge leading to formation of cystic follicles.

  16. T-helper 17 and interleukin-17-producing lymphoid tissue inducer-like cells make different contributions to colitis in mice.

    Science.gov (United States)

    Ono, Yuichi; Kanai, Takanori; Sujino, Tomohisa; Nemoto, Yasuhiro; Kanai, Yasumasa; Mikami, Yohei; Hayashi, Atsushi; Matsumoto, Atsuhiro; Takaishi, Hiromasa; Ogata, Haruhiko; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Watanabe, Mamoru; Hibi, Toshifumi

    2012-11-01

    T helper (Th) 17 cells that express the retinoid-related orphan receptor (ROR) γt contribute to the development of colitis in mice, yet are found in normal and inflamed intestine. We investigated their development and functions in intestines of mice. We analyzed intestinal Th17 cells in healthy and inflamed intestinal tissues of mice. We analyzed expression of lymphotoxin (LT)α by Th17 cells and lymphoid tissue inducer-like cells. LTα(-/-) and RORγt(-/-) mice had significantly lower percentages of naturally occurring Th17 cells in the small intestine than wild-type mice. Numbers of CD3(-)CD4(+/-)interleukin-7Rα(+)c-kit(+)CCR6(+)NKp46(-) lymphoid tissue inducer-like cells that produce interleukin-17A were increased in LTα(-/-) and LTα(-/-) × recombination activating gene (RAG)-2(-/-) mice, compared with wild-type mice, but were absent from RORγt(-/-) mice. Parabiosis of wild-type and LTα(-/-) mice and bone marrow transplant experiments revealed that LTα-dependent gut-associated lymphoid tissue structures are required for generation of naturally occurring Th17 cells. However, when wild-type or LTα(-/-) CD4(+)CD45RB(high) T cells were transferred to RAG-2(-/-) or LTα(-/-)×RAG-2(-/-) mice, all groups, irrespective of the presence or absence of LTα on the donor or recipient cells, developed colitis and generated Th1, Th17, and Th17/Th1 cells. RAG-2(-/-) mice that received a second round of transplantation, with colitogenic but not naturally occurring Th17 cells, developed intestinal inflammation. The presence of naturally occurring Th17 cells in the colons of mice inhibited development of colitis after transfer of CD4(+)CD45RB(high) T cells and increased the numbers of Foxp3(+) cells derived from CD4(+)CD45RB(high) T cells. Gut-associated lymphoid tissue structures are required to generate naturally occurring Th17 cells that have regulatory activities in normal intestines of mice, but not for colitogenic Th17 and Th17/Th1 cells during inflammation

  17. Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.

    Science.gov (United States)

    Ueda, Norihiro; Uemura, Yasushi; Zhang, Rong; Kitayama, Shuichi; Iriguchi, Shoichi; Kawai, Yohei; Yasui, Yutaka; Tatsumi, Minako; Ueda, Tatsuki; Liu, Tian-Yi; Mizoro, Yasutaka; Okada, Chihiro; Watanabe, Akira; Nakanishi, Mahito; Senju, Satoru; Nishimura, Yasuharu; Kuzushima, Kiyotaka; Kiyoi, Hitoshi; Naoe, Tomoki; Kaneko, Shin

    2018-06-05

    CD4 + T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40L high iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40L high iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Permselectivity of blood follicle barriers in mouse ovaries of the mifepristone-induced polycystic ovary model revealed by in vivo cryotechnique.

    Science.gov (United States)

    Zhou, Hong; Ohno, Nobuhiko; Terada, Nobuo; Saitoh, Sei; Naito, Ichiro; Ohno, Shinichi

    2008-11-01

    Despite the potential association of polycystic ovary (PCO) syndrome with hemodynamic changes, follicular microenvironment and the involvement of blood follicle barriers (BFB), a histopathological examination has been hampered by artifacts caused by conventional preparation methods. In this study, mouse ovaries of a mifepristone-induced PCO model were morphologically and immunohistochemically examined by in vivo cryotechnique (IVCT), which prevents those technical artifacts. Ovarian specimens of PCO model mice were prepared by IVCT or the conventional perfusion fixation after s.c. injection of mifepristone. Their histology and immunolocalization of plasma proteins, including albumin (molecular mass, 69 kDa), immunoglobulin G (IgG, 150 kDa), inter-alpha-trypsin inhibitor (ITI, 220 kDa), fibrinogen (340 kDa), and IgM (900 kDa), were examined. In the PCO model, enlarged blood vessels with abundant blood flow were observed in addition to cystic follicles with degenerative membrana granulosa. The immunolocalization of albumin and IgM in the PCO model were similar to those in normal mice. Albumin immunolocalized in the blood vessels, interstitium or follicles, and IgM was mostly restricted within the blood vessels. In contrast, immunolocalization of IgG, ITI, and fibrinogen changed in the PCO model. Both IgG and ITI were clearly blocked by follicular basement membranes, and hardly observed in the membrana granulosa, though fibrinogen was mostly observed within blood vessels. These findings suggest that increased blood flow and enhanced selectivity of molecular permeation through the BFB are prominent features in the PCO ovaries, and changes in hemodynamic conditions and permselectivity of BFB are involved in the pathogenesis and pathophysiology of PCO syndrome.

  19. Innate Lymphoid Cells in Tumor Immunity.

    Science.gov (United States)

    van Beek, Jasper J P; Martens, Anne W J; Bakdash, Ghaith; de Vries, I Jolanda M

    2016-02-25

    Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring.

  20. Disordered follicle development

    Science.gov (United States)

    Chang, R. Jeffrey; Cook-Andersen, Heidi

    2013-01-01

    Alterations of ovarian follicle morphology and function have been well documented in women with PCOS. These include increased numbers of growing preantral follicles, failure of follicle growth beyond the mid-antral stage, evidence of granulosa call degeneration, and theca cell hyperplasia. Functional abnormalities include paradoxical granulosa cell hyperresponsiveness to FSH which is clinically linked to ovarian hyperstimulation during ovulation induction. In addition, there is likely a primary theca cell defect that accounts for the majority of excess androgen production in this disorder. The precise mechanisms responsible for altered follicle function are not completely clear. However, several factors appear to influence normal advancement of follicle development as well as impair ovarian steroidogenesis. These include intra- as well as extraovarian influences that distort normal ovarian growth and disrupt steroid production by follicle cells. PMID:22874072

  1. Stroma cell priming in enteric lymphoid organ morphogenesis

    Directory of Open Access Journals (Sweden)

    Manuela eFerreira

    2012-07-01

    Full Text Available The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional Lymphoid Tissue inducer (LTi cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to secondary lymphoid organ formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood.

  2. Amenorrhea secondary to a vismodegib-induced blockade of follicle-stimulating hormone-receptor activation.

    Science.gov (United States)

    Strasswimmer, John; Latimer, Benjamin; Ory, Steven

    2014-08-01

    To report a novel mechanism suggestive of early ovarian failure secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib. Case report and literature review. Academic and private dermatology and fertility practices. A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib. Physical examination and endocrine evaluation. Elevated follicle-stimulating hormone (FSH) and low estrogen in the setting of a normal anti-Müllerian hormone. FSH was elevated; estrogen was low. Preantral follicles were detected and anti-Müllerian hormone activity was normal. Menses resumed 5 weeks after cessation of therapy. Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway is indicated for advanced basal cell carcinoma and is associated with amenorrhea. The mechanism is unknown; it has some features of ovarian failure but preserves ovarian potential through blockading of FSH-receptor-dependent signal transduction. This effect appears to be rapidly reversible upon cessation of therapy. Vismodegib and related compounds may have potential for a role in intervention for gynecologic and endocrine disorders and in therapy for other issues involving FSH-dependent function. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Amniotic fluid stem cells prevent follicle atresia and rescue fertility of mice with premature ovarian failure induced by chemotherapy.

    Science.gov (United States)

    Xiao, Guan-Yu; Liu, I-Hsuan; Cheng, Chun-Chun; Chang, Chia-Chun; Lee, Yen-Hua; Cheng, Winston Teng-Kuei; Wu, Shinn-Chih

    2014-01-01

    Chemotherapy used to treat cancer may cause irreversible premature ovarian failure (POF). Of late, amniotic fluid stem cells (AFSCs) provide a novel source for regenerative medicine because of their primitive stage, low immunogenicity, and easy accessibility. In this study, we isolated AFSCs from transgenic mice that ubiquitously express enhanced green fluorescence protein (EGFP). These AFSCs exhibited morphologies, immunophenotypes, and mesoderm trilineage differentiation potentials similar to mesenchymal stem cells (MSCs). Further, AFSCs proliferated faster than MSCs and expressed OCT4, a marker for pluripotency. To investigate their potential in recovering fertility in POF model, AFSCs were transplanted into the ovaries of mice with POF six weeks post induction using chemotherapeutic drugs, busulfan and cyclophosphamide. AFSCs could rescue the reproductive ability of mice with POF by preventing follicle atresia and sustaining the healthy follicles. Notably, the transplanted AFSCs did not differentiate into granulosa and germline cells in vivo. After one month, the decreased numbers of transplanted AFSCs accompanied with the reduced beneficial effects indicated that the therapeutic efficacy were directly from AFSCs. These findings demonstrated the therapeutic effects of AFSCs and suggested the promise of AFSCs for treating infertility and POF caused by chemotherapy.

  4. Amniotic fluid stem cells prevent follicle atresia and rescue fertility of mice with premature ovarian failure induced by chemotherapy.

    Directory of Open Access Journals (Sweden)

    Guan-Yu Xiao

    Full Text Available Chemotherapy used to treat cancer may cause irreversible premature ovarian failure (POF. Of late, amniotic fluid stem cells (AFSCs provide a novel source for regenerative medicine because of their primitive stage, low immunogenicity, and easy accessibility. In this study, we isolated AFSCs from transgenic mice that ubiquitously express enhanced green fluorescence protein (EGFP. These AFSCs exhibited morphologies, immunophenotypes, and mesoderm trilineage differentiation potentials similar to mesenchymal stem cells (MSCs. Further, AFSCs proliferated faster than MSCs and expressed OCT4, a marker for pluripotency. To investigate their potential in recovering fertility in POF model, AFSCs were transplanted into the ovaries of mice with POF six weeks post induction using chemotherapeutic drugs, busulfan and cyclophosphamide. AFSCs could rescue the reproductive ability of mice with POF by preventing follicle atresia and sustaining the healthy follicles. Notably, the transplanted AFSCs did not differentiate into granulosa and germline cells in vivo. After one month, the decreased numbers of transplanted AFSCs accompanied with the reduced beneficial effects indicated that the therapeutic efficacy were directly from AFSCs. These findings demonstrated the therapeutic effects of AFSCs and suggested the promise of AFSCs for treating infertility and POF caused by chemotherapy.

  5. Increased prevalence of lymphoid tissue inducer cells in the cerebrospinal fluid of patients with early multiple sclerosis

    DEFF Research Database (Denmark)

    Degn, Matilda; Modvig, Signe; Dyring-Andersen, Beatrice

    2016-01-01

    BACKGROUND: Inflammatory cytokines produced by cells of the immune system are believed to play a central role in the pathogenesis of multiple sclerosis (MS). Innate lymphoid cells (ILCs) have been shown to produce and secrete a wide range of the cytokines involved in MS pathogenesis; however...... of LTi cells in the CSF, suggesting a favoured recruitment of blood derived LTi cells. CONCLUSION: Our data suggests a role for ILCs, and in particular the LTi subset, in the early stages of MS. This finding represents an important contribution to the understanding of early inflammation in MS, and adds...

  6. Activation of human B lymphocytes. 8. Differential radiosensitivity of subpopulations of lymphoid cells involved in the polyclonally-induced PFC responses of peripheral blood B lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Fauci, A S; Pratt, K R; Whalen, G [National Inst. of Allergy and Infectious Diseases, Bethesda, MD (USA)

    1978-11-01

    The differential effect of various doses of irradiation on subpopulations of human peripheral blood lymphoid cells involved in the pokeweed mitogen induced PFC response against sheep red blood cells was studied. The plaque forming B cells were quite sensitive to low doses of irradiation with complete suppression of responses at 300 to 500 rad. On the contrary, helper T-cell function was resistant to 2000 rad. Co-culture of irradiated T cells with autologous or allogeneic B cells resulted in marked enhancement of PFC responses consistent with the suppression of naturally occurring suppressor cells with a resulting pure helper effect. Irradiated T-cell-depleted suspensions failed to produce this effect as did heat killed T cells, whereas mitomycin C treated T cells gave effects similar to irradiated T cells. These findings are consistent with a lack of requirement of cell division for a T-cell helper effect and a requirement of mitosis or another irradiation sensitive, mitomycin C sensitive process for a T-suppressor cell effect. These studies have potential relevance in the evaluation of subpopulations of human lymphoid cells involved in antibody production in normal individuals and in disease states.

  7. Benzo[a]pyrene-induced immunotoxicity in Japanese medaka (Oryzias latipes): relationship between lymphoid CYP1A activity and humoral immune suppression

    International Nuclear Information System (INIS)

    Carlson, E.A.; Li, Y.; Zelikoff, J.T.

    2004-01-01

    Exposure to the environmental contaminant benzo[a]pyrene (BaP) results in suppression of immune function in both mammalian and fish species. This laboratory has previously demonstrated that a single intraperitoneal (IP) injection of BaP reduced lymphocyte proliferation, phagocyte-mediated superoxide generation, and antibody-forming cell (AFC) numbers in Japanese medaka (Oryzias latipes). The objective of the current study was to determine the role of BaP metabolism in the observed immunosuppression. Results from rodent studies have suggested that BaP elicits its immunotoxic effects via upregulation of cytochrome P4501A1 (CYP1A1) and the subsequent production of immunosuppressive BaP metabolites. In this study, exposure of medaka to 200 μg BaP/g BW significantly induced CYP1A expression or activity within lymphoid tissue 48 h post-IP injection; induction was observed specifically within distinct subpopulations of kidney mononuclear cells. Concurrent injection of fish with BaP and the CYP1A1 inhibitors α-naphthoflavone (ANF) or dehydroepiandrosterone (DHEA) resulted in inhibition of renal EROD activity and amelioration of BaP-induced suppression of medaka AFC numbers. Results of this study suggest that (1) BaP-induced suppression of medaka humoral immunity relies upon the CYP1A-catalyzed production of immunotoxic BaP metabolites and (2) BaP metabolites may be created in situ, directly by specific cells within kidney lymphoid tissue. Thus, apparently, mechanisms involved in BaP-induced immunosuppression have been phylogenetically conserved from fish to mammals

  8. Human innate lymphoid cells

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Spits, Hergen

    2014-01-01

    Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of

  9. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    DEFF Research Database (Denmark)

    Sørensen, C.M.; Holmskov, U.; Aalbæk, B.

    2005-01-01

    , the absence of macrophage marker immunoreactivity and the presence of dendritic cell marker immunoreactivity. Increased expression of pSP-D in the surfactant coincided with presence of pSP-D-positive dendritic cells in bronchus-associated lymphoid tissue (BALT), indicating a possible transport of p...... and with dendritic cells in microbial-induced BALT. The function of the interaction between pSP-D and dendritic cells in BALT remain unclear, but pSP-D could represent a link between the innate and adaptive immune system, facilitating the bacterial antigen presentation by dendritic cells in BALT.......Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic...

  10. Characterization of membranous (M) cells in normal feline conjunctiva-associated lymphoid tissue (CALT).

    Science.gov (United States)

    Giuliano, Elizabeth A; Finn, Kevin

    2011-09-01

    To characterize conjunctival lymphoid nodules obtained from the nictitans of healthy cats to determine if the follicle-associated epithelium (FAE) of conjunctiva-associated lymphoid tissue (CALT) in this species contains membranous (M)-cells analogous to those described in other regions of mucosa-associated lymphoid tissue (MALT). Lymphoid follicles from nictitan bulbar surfaces of 10 healthy cats (20 eyes total) were examined. Nictitans from five cats were harvested immediately post-mortem and a minimum of 12 lymphoid nodules from each third eyelid were isolated using a Zeiss operating microscope. At least three lymphoid follicles from each eye were examined using light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) using standard fixation and embedding protocols. Nictitan-lymphoid follicles from another five healthy cats were processed for immunohistochemistry to characterize the distribution of T- and B-lymphocytes present beneath the FAE. The FAE overlying CALT from 10 healthy cats demonstrated morphology characteristic of M-cells including attenuated apical cell surface with blunted microvilli and microfolds, invaginated basolateral membrane forming a cytoplasmic pocket, and diminished distance between the apical and pocket membrane. Immunohistochemistry of lymphoid tissue subtending the FAE demonstrated B-cell dependent regions in the germinal centers surrounded by T-cell dependent interfollicular zones. Healthy feline CALT contains morphologic features analogous to those described in other regions of MALT. Documentation of feline conjunctival M-cells is of clinical relevance in the study of primary infectious, allergic, and autoimmune ocular diseases, as well as a potential means of vaccination or drug delivery. © 2011 American College of Veterinary Ophthalmologists.

  11. Innate lymphoid cells in atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-12-05

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  12. Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.

    Science.gov (United States)

    Egbert, Jeremy R; Yee, Siu-Pok; Jaffe, Laurinda A

    2018-03-01

    Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Immunophenotype of cells within cervine rectoanal mucosa-associated lymphoid tissue and mesenteric lymph nodes.

    Science.gov (United States)

    Dagleish, M P; Finlayson, J; Steele, P J; Pang, Y; Hamilton, S; Eaton, S L; Sales, J; González, L; Chianini, F

    2012-05-01

    Rectoanal mucosa-associated lymphoid tissue (RAMALT) is a part of the lymphoid system that can be sampled easily in live animals, especially ruminants. RAMALT biopsy is useful for the diagnosis of transmissible spongiform encephalopathies, including scrapie in sheep and goats and chronic wasting disease (CWD) in cervids. Diagnosis is reliant on detection of abnormal prion protein (PrP(d)), which is associated with lymphoid follicles. For enzyme linked immunosorbent assays (ELISAs) detecting PrP(d) it is necessary to ensure that lymphoid follicles are present in biopsy samples to avoid false-negative results. Monoclonal antibodies known to recognize specific immune cell subsets present in lymphoid tissues of sheep were tested for cross-reactivity with cervine RAMALT and mesenteric lymph nodes (MLNs) preserved in zinc salts fixative. The distribution of cells expressing CD3, CD4, CD79, CD21 and class II molecules of the major histocompatibility complex was determined in these tissues. Cells of each immunophenotype had similar distributions in RAMALT and MLNs and these distributions were similar to those reported previously for sheep and cattle. The identification and validation of cervine lymphoid follicle cell markers (CD79 and CD21) may allow reduction in false-negative results during diagnosis of CWD by ELISA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly

    Directory of Open Access Journals (Sweden)

    Deepa Bhartiya

    2016-01-01

    Full Text Available Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes. These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility.

  15. Evidence for gating roles of protein kinase A and protein kinase C in estradiol-induced luteinizing hormone receptor (lhcgr) expression in zebrafish ovarian follicle cells.

    Science.gov (United States)

    Liu, Ka-Cheuk; Ge, Wei

    2013-01-01

    Estradiol (E2) stimulates luteinizing hormone receptor (lhcgr) expression in zebrafish follicle cells via nuclear estrogen receptors (nERs) that are likely expressed on the membrane, and lhcgr responds to E2 in a biphasic manner during 24-h treatment. These observations raise an interesting question on the signaling mechanism underlying E2 regulation, in particular the biphasic response of lhcgr expression. In the present study, we demonstrated that E2 regulation of lhcgr was significantly influenced by the activity of cAMP-PKA pathway. Activation of cAMP-PKA pathway by forskolin or db-cAMP suppressed E2-stimulated lhcgr expression in short-term (3 h) but enhanced its effect in long-term (24 h), suggesting differential roles of PKA at these two phases of lhcgr response. PKA inhibitor H89 showed reversed effects. In contrast, PKC pathway had consistent permissive effect on E2-induced lhcgr expression as evidenced by strong inhibition of E2 effect by PKC inhibitors GF109203X and Ro-31-8220 at both 3 and 24 h. One of the mechanisms by which PKA and PKC gated E2 effect might be through regulating nERs, particularly esr2a. Despite the strong influence of PKA and PKC, our data did not suggest direct mediating roles for these two pathways in E2 stimulation of lhcgr expression; yet they likely play critical gating roles in E2 signal transduction. As a follow-up study to our previous report on E2 regulation of gonadotropin receptors in the zebrafish ovary, the present study provides further evidence for the involvement of classical intracellular signal transduction pathways in E2 stimulation of lhcgr expression in the follicle cells.

  16. Identifying a novel role for X-prolyl aminopeptidase (Xpnpep) 2 in CrVI-induced adverse effects on germ cell nest breakdown and follicle development in rats.

    Science.gov (United States)

    Banu, Sakhila K; Stanley, Jone A; Sivakumar, Kirthiram K; Arosh, Joe A; Barhoumi, Rola; Burghardt, Robert C

    2015-03-01

    Environmental exposure to endocrine-disrupting chemicals (EDCs) is one cause of premature ovarian failure (POF). Hexavalent chromium (CrVI) is a heavy metal EDC widely used in more than 50 industries, including chrome plating, welding, wood processing, and tanneries. Recent data from U.S. Environmental Protection Agency indicate increased levels of Cr in drinking water from several American cities, which potentially predispose residents to various health problems. Recently, we demonstrated that gestational exposure to CrVI caused POF in F1 offspring. The current study was performed to identify the molecular mechanism behind CrVI-induced POF. Pregnant rats were treated with 25 ppm of potassium dichromate from Gestational Day (GD) 9.5 to GD 14.5 through drinking water, and the fetuses were exposed to CrVI through transplacental transfer. Ovaries were removed from the fetuses or pups on Embryonic Day (ED) 15.5, ED 17.5, Postnatal Day (PND) 1, PND 4, or PND 25, and various analyses were performed. Results showed that gestational exposure to CrVI: 1) increased germ cell/oocyte apoptosis and advanced germ cell nest (GCN) breakdown; 2) increased X-prolyl aminopeptidase (Xpnpep) 2, a POF marker in humans, during GCN breakdown; 3) decreased Xpnpep2 during postnatal follicle development; and 4) increased colocalization of Xpnpep2 with Col3 and Col4. We also found that Xpnpep2 inversely regulated the expression of Col1, Col3, and Col4 in all the developmental stages studied. Thus, CrVI advanced GCN breakdown and increased follicle atresia in F1 female progeny by targeting Xpnpep2. © 2015 by the Society for the Study of Reproduction, Inc.

  17. Stromal cell regulation of homeostatic and inflammatory lymphoid organogenesis

    Science.gov (United States)

    Kain, Matthew J W; Owens, Benjamin M J

    2013-01-01

    Summary Secondary lymphoid organs function to increase the efficiency of interactions between rare, antigen-specific lymphocytes and antigen presenting cells, concentrating antigen and lymphocytes in a supportive environment that facilitates the initiation of an adaptive immune response. Homeostatic lymphoid tissue organogenesis proceeds via exquisitely controlled spatiotemporal interactions between haematopoietic lymphoid tissue inducer populations and multiple subsets of non-haematopoietic stromal cells. However, it is becoming clear that in a range of inflammatory contexts, ectopic or tertiary lymphoid tissues can develop inappropriately under pathological stress. Here we summarize the role of stromal cells in the development of homeostatic lymphoid tissue, and assess emerging evidence that suggests a critical role for stromal involvement in the tertiary lymphoid tissue development associated with chronic infections and inflammation. PMID:23621403

  18. Effects of Thy-1+ cell depletion on the capacity of donor lymphoid cells to induce tolerance across an entire MHC disparity in sublethally irradiated adult hosts

    International Nuclear Information System (INIS)

    Pierce, G.E.; Watts, L.M.

    1989-01-01

    Thy-1+ cell depletion with anti-Thy-1.2 mAb and complement markedly reduced the capacity of C57BL/6J, H-2b bone marrow to establish mixed lymphoid chimerism and induce tolerance to C57BL/6J skin grafts across an entire MHC disparity in BALB/c, H-2d hosts conditioned with sublethal, fractionated 7.5 Gy total-body irradiation. In this model tolerance can be transferred to secondary irradiated BALB/c hosts only by cells of C57BL/6J donor, not host, genotype isolated from the spleens of tolerant hosts. Thy-1+ cell depletion abolished the capacity of C57BL/6J donor cells from tolerant BALB/c host spleens to transfer tolerance. The capacity of semiallogeneic BALB/c x C57BL/6J F1, H-2d/b donor BM and spleen cells to induce chimerism and tolerance to C57BL/6J skin grafts in BALB/c parental hosts was also reduced by Thy-1+ cell depletion. Thus the requirement for donor Thy-1+ cells cannot be explained simply on the basis of alloaggression. It is unlikely that the requisite Thy-1+ cells are nonspecific suppressor cells: Thy-1+ cell depletion had no effect on the slight but significant prolongation of third-party C3H/HeJ, H-2k skin grafts in irradiated BALB/c hosts injected with allogeneic C57BL/6J or semiallogeneic BALB/c x C57BL/6J F1 BM compared to irradiated controls injected with medium only. Furthermore, injections of semiallogeneic F1 spleen cells had no significant effect on the survival of the third-party grafts, although these cells were fully capable of inducing tolerance, and their capacity to induce tolerance was significantly reduced by Thy-1+ cell depletion. The requirement for a specific population of lymphoid cells, i.e. Thy-1+, remains unexplained but suggests that donor cells might play a role in the induction or maintenance of tolerance in this model other than merely providing a circulating source of donor antigens

  19. Morphological anomaly of primordial follicle in {gamma}-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Lee, Chang Joo; Lee, Young Dal [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1999-08-01

    Ovarian follicles are faced with one of two fates, atresia or development. Up to 99% of follicles become degenerated rather than ovulated in female life span. Thus, atresia occurs at all stages of follicle development in mammalian ovaries. In the present experiment, the effect of {gamma}-radiation on primordial follicles was morphologically analyzed in a mouse ovary. Thirty-seven percent of the primordial follicles in the non-irradiated control mice ovaries were abnormal. At day 8 post irradiation, most of primordial follicles became atretic. They lost their integrity of architecture in the follicular shape. Then, all the oocytes disappeared from the follicles. And only 3 to 4 granulosa cells lay down onto the basement membrane. Disappearance of granulosa cells or oocytes resulted from the radiation-induced apoptotic process. It is definitely clear that {gamma}-radiation induces rapid apoptotic degeneration of the primordial follicles. The morphological degeneration induced by radiation in the primordial follicles can be used as an experimental model to draw out a deeper insight for radioprotectant researches. (author). 22 refs., 4 figs.

  20. Lymphoid Aggregates That Resemble Tertiary Lymphoid Organs Define a Specific Pathological Subset in Metal-on-Metal Hip Replacements

    Science.gov (United States)

    Barone, Francesca; Hardie, Debbie L.; Matharu, Gulraj S.; Davenport, Alison J.; Martin, Richard A.; Grant, Melissa; Mosselmans, Frederick; Pynsent, Paul; Sumathi, Vaiyapuri P.; Addison, Owen; Revell, Peter A.; Buckley, Christopher D.

    2013-01-01

    Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) has been used to describe the histological lesion associated with metal-on-metal (M-M) bearings. We tested the hypothesis that the lymphoid aggregates, associated with ALVAL lesions resemble tertiary lymphoid organs (TLOs). Histopathological changes were examined in the periprosthetic tissue of 62 M-M hip replacements requiring revision surgery, with particular emphasis on the characteristics and pattern of the lymphocytic infiltrate. Immunofluorescence and immunohistochemistry were used to study the classical features of TLOs in cases where large organized lymphoid follicles were present. Synchrotron X-ray fluorescence (XRF) measurements were undertaken to detect localisation of implant derived ions/particles within the samples. Based on type of lymphocytic infiltrates, three different categories were recognised; diffuse aggregates (51%), T cell aggregates (20%), and organised lymphoid aggregates (29%). Further investigation of tissues with organised lymphoid aggregates showed that these tissues recapitulate many of the features of TLOs with T cells and B cells organised into discrete areas, the presence of follicular dendritic cells, acquisition of high endothelial venule like phenotype by blood vessels, expression of lymphoid chemokines and the presence of plasma cells. Co-localisation of implant-derived metals with lymphoid aggregates was observed. These findings suggest that in addition to the well described general foreign body reaction mediated by macrophages and a T cell mediated type IV hypersensitivity response, an under-recognized immunological reaction to metal wear debris involving B cells and the formation of tertiary lymphoid organs occurs in a distinct subset of patients with M-M implants. PMID:23723985

  1. Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Slavin, S.; Morecki, S.; Weigensberg, M.; Bar, S.; Weiss, L.

    1986-01-01

    Allogeneic bone marrow (BM) chimeras induced by infusion of BM cells into recipients conditioned with total lymphoid irradiation (TLI) were shown to develop humoral and cell-mediated tolerance to host and donor-type alloantigens by a number of in vitro and in vivo assays. Spleen cells of tolerant chimeras exhibited suppressive activity of mixed lymphocyte reaction (MLR). MLR suppression was not abrogated by depletion of Lyt-2 cells, and neither could Lyt-2-positive cells sorted from the spleens of tolerant chimeras suppress MLR or attenuate graft-versus-host reactivity in vivo. Likewise, specifically unresponsive spleen cells obtained from chimeras could not be induced to respond in MLR against tolerizing host-type cells following depletion of Lyt-2 or passage through a nylon-wool column. Tolerance of chimera spleen cells to host alloantigens, best documented by permanent survival of donor-type skin allografts, could be adoptively transferred into syngeneic recipients treated by heavy irradiation but not into untreated or mildly irradiated recipients. Adoptive transfer of tolerance seemed to be associated with experimental conditions favoring engraftment of tolerant cells rather than suppression of host reactivity. We speculate that although host and/or donor-derived suppressor cells may be operating in reducing the pool of specific alloreactive clones by blocking cell proliferation in response to allogeneic challenge, the final outcome in tolerant chimeras is actual or functional deletion of alloreactive clones

  2. Functional differences between human NKp44(-) and NKp44(+) RORC+ innate lymphoid cells

    NARCIS (Netherlands)

    Hoorweg, Kerim; Peters, Charlotte P.; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M.; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human

  3. Hair follicle proteoglycans

    DEFF Research Database (Denmark)

    Couchman, J R

    1993-01-01

    that are present in the epithelial and stromal compartments of hair follicles. However, the transmembrane proteoglycan syndecan may be important in follicle morphogenesis, both with respect to the epithelium and dermal papilla cells. Syndecan may possess both heparan and chondroitin sulfate chains, interacts...... basement membranes, including those surrounding the epithelial compartment of hair follicles. Additionally, and quite unlike the dermis, the dermal papilla is enriched in basement-membrane components, especially a chondroitin 6-sulfate-containing proteoglycan, BM-CSPG. The function of this proteoglycan...... is not known, but developmental studies indicate that it may have a role in stabilizing basement membranes. In the hair cycle, BM-CSPG decreases through catagen and is virtually absent from the telogen papilla. One or more heparan sulfate proteoglycans, including perlecan, are also present in papilla...

  4. Nrf2 pathway modulates Substance P-induced human mast cell activation and degranulation in the hair follicle.

    Science.gov (United States)

    Jadkauskaite, Laura; Bahri, Rajia; Farjo, Nilofer; Farjo, Bessam; Jenkins, Gail; Bhogal, Ranjit; Haslam, Iain; Bulfone-Paus, Silvia; Paus, Ralf

    2018-05-30

    Activation of Nrf2 in primary human mast cells exposed to oxidative stress induced by substance P suppresses pro-inflammatory gene transcription, activation and degranulation. Copyright © 2018. Published by Elsevier Inc.

  5. Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells

    International Nuclear Information System (INIS)

    Singh, A.; Singh, A.; Sand, J. M.; Bin Hafeez, B.; Verma, A. K.; Sand, J. M.; Heninger, E.

    2013-01-01

    To find clues about the mechanism by which kinase C epsilon (PKCε) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKCε transgenic (TG) mice and their wild-type (WT) litter mates for (1) the effects of UVR exposures on percent of putative hair follicle stem cells (HSC s ) and (2) HSCs proliferation. The percent of double HSC s (CD34+ andα6-integrin or CD34+/CD49f+) in the isolated keratinocytes were determined by flow cytometric analysis. Both single and chronic UVR treatments (1.8 kJ/m 2 ) resulted in an increase in the frequency of double positive HSCs in PKCεTG mice as compared to their WT litter mates. To determine the rate of proliferation of bulge region stem cells, a 5-bromo-2-deoxyuridine labeling (BrdU) experiment was performed. In the WT mice, the percent of double positive HSC s retaining BrdU label was 28.4±0.6% compared to 4.0±0.06% for the TG mice, an approximately 7-fold decrease. A comparison of gene expression profiles of FACS sorted double positive HSCs showed increased expression of Pes1, Rad21, Tfdp1 and Cks1b genes in TG mice compared to WT mice. Also, PKCεover expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells.

  6. Characterization of nasal cavity-associated lymphoid tissue in ducks.

    Science.gov (United States)

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2014-05-01

    The nasal mucosa is involved in immune defense, as it is the first barrier for pathogens entering the body through the respiratory tract. The nasal cavity-associated lymphoid tissue (NALT), which is found in the mucosa of the nasal cavity, is considered to be the main mucosal immune inductive site in the upper respiratory tract. NALT has been found in humans and many mammals, which contributes to local and systemic immune responses after intranasal vaccination. However, there are very few data on NALT in avian species, especially waterfowl. For this study, histological sections of the nasal cavities of Cherry Valley ducks were used to examine the anatomical location and histological characteristics of NALT. The results showed that several lymphoid aggregates are present in the ventral wall of the nasal cavity near the choanal cleft, whereas several more lymphoid aggregates were located on both sides of the nasal septum. In addition, randomly distributed intraepithelial lymphocytes and isolated lymphoid follicles were observed in the regio respiratoria of the nasal cavity. There were also a few lymphoid aggregates located in the lamina propria of the regio vestibularis, which was covered with a stratified squamous epithelium. This study focused on the anatomic and histological characteristics of the nasal cavity of the duck and performed a systemic overview of NALT. This will be beneficial for further understanding of immune mechanisms after nasal vaccination and the development of effective nasal vaccines for waterfowls. Copyright © 2014 Wiley Periodicals, Inc.

  7. Role of Tertiary Lymphoid Structures (TLS) in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Pimenta, Erica M. [Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States); Barnes, Betsy J., E-mail: barnesbe@njms.rutgers.edu [Department of Biochemistry and Molecular Biology, Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States)

    2014-04-23

    Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin{sup ®}) and rituximab (Rituxan{sup ®})) and the first approved cancer vaccine, Provenge{sup ®} (sipuleucel-T), investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS) within the tumor microenvironment may be used to enhance immunotherapy response.

  8. Role of Tertiary Lymphoid Structures (TLS in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

    Directory of Open Access Journals (Sweden)

    Erica M. Pimenta

    2014-04-01

    Full Text Available Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin® and rituximab (Rituxan® and the first approved cancer vaccine, Provenge® (sipuleucel-T, investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS within the tumor microenvironment may be used to enhance immunotherapy response.

  9. Isolation of Human Innate Lymphoid Cells.

    Science.gov (United States)

    Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M

    2018-06-29

    Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

  10. Bronchial lesions of mouse model of asthma are preceded by immune complex vasculitis and induced bronchial associated lymphoid tissue (iBALT).

    Science.gov (United States)

    Guest, Ian C; Sell, Stewart

    2015-08-01

    We systematically examined by immune histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 h after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin (Ig) and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy (GCHT). After two challenges, severe eosinophilic vasculitis is present at 6 h, increases by 72 h, and then declines; B-cell proliferation and significant GCHT and hyperplasia (GCHTH) and bronchial smooth muscle hypertrophy recur more prominently. After three challenges, there is significantly increased induced bronchus-associated lymphoid tissue (iBALT) formation, GCHTH, and smooth muscle hypertrophy. Elevated levels of Th2 cytokines, IL-4, IL-5, and IL-13, are present in bronchial lavage fluids. Sensitized mice have precipitating antibody and positive Arthus skin reactions but also develop significant levels of IgE antibody to OVA but only 1 week after challenge. We conclude that the asthma like lung lesions induced in these models is preceded by immune complex-mediated eosinophilic vasculitis and iBALT formation. There are elevations of Th2 cytokines that most likely produce bronchial lesions that resemble human asthma. However, it is unlikely that mast cell-activated atopic mechanisms are responsible as we found only a few presumed mast cells by toluidine blue and metachromatic staining limited to the most proximal part of the main stem bronchus, and none in the remaining main stem bronchus or in the lung periphery.

  11. Human innate lymphoid cells.

    Science.gov (United States)

    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Human innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2016-01-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune

  13. Disease-associated prion protein in neural and lymphoid tissues of mink (Mustela vison) inoculated with transmissible mink encephalopathy.

    Science.gov (United States)

    Schneider, D A; Harrington, R D; Zhuang, D; Yan, H; Truscott, T C; Dassanayake, R P; O'Rourke, K I

    2012-11-01

    Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrP(d)). The distribution of PrP(d) within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrP(TME) and of which only the HY strain is associated with accumulation of PrP(TME) in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrP(TME) in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum, after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrP(TME) was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrP(TME) was detected readily in the brain and retropharyngeal lymph node during preclinical infection, with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrP(TME) in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrP(TME) accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrP(TME) in the lymphoid

  14. Acute lymphoid and gastrointestinal toxicity induced by selective p38alpha map kinase and map kinase-activated protein kinase-2 (MK2) inhibitors in the dog.

    Science.gov (United States)

    Morris, Dale L; O'Neil, Shawn P; Devraj, Rajesh V; Portanova, Joseph P; Gilles, Richard W; Gross, Cindy J; Curtiss, Sandra W; Komocsar, Wendy J; Garner, Debra S; Happa, Fernando A; Kraus, Lori J; Nikula, Kristen J; Monahan, Joseph B; Selness, Shaun R; Galluppi, Gerald R; Shevlin, Kimberly M; Kramer, Jeffrey A; Walker, John K; Messing, Dean M; Anderson, David R; Mourey, Robert J; Whiteley, Laurence O; Daniels, John S; Yang, Jerry Z; Rowlands, Philip C; Alden, Carl L; Davis, John W; Sagartz, John E

    2010-06-01

    Exposure to moderately selective p38alpha mitogen-activated protein kinase (MAPK) inhibitors in the Beagle dog results in an acute toxicity consisting of mild clinical signs (decreased activity, diarrhea, and fever), lymphoid necrosis and depletion in the gut-associated lymphoid tissue (GALT), mesenteric lymph nodes and spleen, and linear colonic and cecal mucosal hemorrhages. Lymphocyte apoptosis and necrosis in the GALT is the earliest and most prominent histopathologic change observed, followed temporally by neutrophilic infiltration and acute inflammation of the lymph nodes and spleen and multifocal mucosal epithelial necrosis and linear hemorrhages in the colon and cecum. These effects are not observed in the mouse, rat, or cynomolgus monkey. To further characterize the acute toxicity in the dog, a series of in vivo, in vitro, and immunohistochemical studies were conducted to determine the relationship between the lymphoid and gastrointestinal (GI) toxicity and p38 MAPK inhibition. Results of these studies demonstrate a direct correlation between p38alpha MAPK inhibition and the acute lymphoid and gastrointestinal toxicity in the dog. Similar effects were observed following exposure to inhibitors of MAPK-activated protein kinase-2 (MK2), further implicating the role of p38alpha MAPK signaling pathway inhibition in these effects. Based on these findings, the authors conclude that p38alpha MAPK inhibition results in acute lymphoid and GI toxicity in the dog and is unique among the species evaluated in these studies.

  15. Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosal associated lymphoid tissues from elk by real time quaking-induced conversion

    Science.gov (United States)

    Haley, Nicholas J.; Siepker, Chris; Hoon-Hanks , Laura L.; Mitchell, Gordon; Walter, W. David; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen a.; Fenwick, B.W.

    2016-01-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

  16. Sinomenine suppresses collagen-induced arthritis by reciprocal modulation of regulatory T cells and Th17 cells in gut-associated lymphoid tissues.

    Science.gov (United States)

    Tong, Bei; Yu, Juntao; Wang, Ting; Dou, Yannong; Wu, Xin; Kong, Lingyi; Dai, Yue; Xia, Yufeng

    2015-05-01

    Sinomenine (SIN) has long been used as a therapeutic agent of rheumatoid arthritis (RA) in China. However, the discrepancy between low oral bioavailability and higher minimal effective concentration made its action mode mysterious. The present study aimed to gain insight into the mechanisms by which SIN suppressed collagen-induced arthritis (CIA) in rats in view of Th17 and regulatory T (Treg) cell balance. SIN was orally administered, and the clinical symptoms of CIA rats were monitored; inflammatory cytokines levels in serum were measured by ELISA; pharmacokinetic studies were performed in normal and CIA rats; Th17 and Treg cell frequencies were analyzed by flow cytometry. The data showed that SIN treatment resulted in a dramatic decrease of arthritis scores and paw volume of CIA rats, which was accompanied by down-regulation of IL-17A and up-regulation of IL-10 in rat serum. The frequency of Treg cells was increased and the frequency of Th17 cells was decreased in the gut lymphoid tissues of SIN-treated rats. Immunohistochemistry assay demonstrated that more α4β7-positive cells were detained in joint tissues after SIN treatment. Moreover, the anti-arthritis efficacy of SIN disappeared when it was given by intraperitoneal injection, further confirming the action of SIN was gut-dependent. In conclusion, SIN exerts anti-RA action probably through modulating the frequencies of Treg cells and Th17 cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from gut to joint. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma with a Nodular Opacity: Report of a Case.

    Science.gov (United States)

    Yoshino, Naoyuki; Hirata, Tomomi; Takeuchi, Chie; Usuda, Jitsuo; Hosone, Masaru

    2017-01-01

    Herein, we describe our experience in treating a case of primary pulmonary mucosa-associated lymphoid tissue lymphoma detected as a nodular opacity. A 79-year-old man was referred to our hospital. Computed tomography showed a nodular opacity measuring 20 mm in diameter with regular margins in segment 5 of the right middle lobe of the lung. Although the bronchoscopic brush cytology result was class III, the patient was tentatively diagnosed with suspected mucosa-associated lymphoid tissue lymphoma. A thoracoscopic right middle lobectomy was performed. The pathological findings showed nodular proliferation of small to medium-sized, mature-appearing atypical lymphoid cells, lymphoepithelial lesions, and vague follicles suggesting follicular colonization in some areas. The patient was diagnosed with low-grade small B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. He has remained well to date, 23 months after surgery, without evidence of recurrence.

  18. Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.

    Science.gov (United States)

    Goverse, Gera; Labao-Almeida, Carlos; Ferreira, Manuela; Molenaar, Rosalie; Wahlen, Sigrid; Konijn, Tanja; Koning, Jasper; Veiga-Fernandes, Henrique; Mebius, Reina E

    2016-06-15

    Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines. Copyright © 2016 by The American Association of Immunologists, Inc.

  19. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. © FASEB.

  20. Effects of follicle stimulationg hormone on {gamma}-ray irradiated immature mouse ovarian follicles

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Lee, Chang Joo; Lee, Young Keun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Song, Kang Won; Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    1998-06-01

    To assess the radioprotective effects of Follicle Stimulating Hormone (FSH) on ovarian follicles, 3 week-old female mice were irradiated with 8.33 Gy of {gamma}-ray (group R) and followed by 5 IU ip-injection of FSH (group RF). For control groups, 5 IU of saline (group C) or 5 IU of FSH (group F) was ip-injected. Ovaries were collected 0h, 6h, 12h, 1d, 2d, 4d, and 8d after irradiation or saline/FSH injection, and followed by fixation in neutral buffered formalin for routine histochemistry. Immunohistochemistry was used to assess the status of follicles and DNA fragmentation was analyzed by agarose gel electrophoresis for total DNA. Staining specific for apoptotic follicles showed high intensity at 6h and 12h in group R and RF. On the other hand, staining specific for proliferating follicles showed noticeably high intensity at 8d in group R and RF. DNA fragmentation of 185bp increased with time in all experimental groups. Especially 370bp appeared at 6h in group R, then disappeared after 1d. In case of group RF, it appeared at 12h and disappeared after 1d. From the above results, the irradiated antral follicles become completely disappeared from 4d to 8d, and then new follicles started to grow again at 8d. FSH had delaying or suppressing effects on follicular atresia after irradiation. In addition, it became clear that radiation-induced follicular atresia was mediated by granulosa cell apoptosis.

  1. Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis.

    Science.gov (United States)

    Sanches, Françoise P; Tomokane, Thaise Y; Da Matta, Vânia L R; Marcondes, Mary; Corbett, Carlos E P; Laurenti, Márcia D

    2014-09-07

    There are only a few studies reporting the role of nitric oxide metabolites for controlling macrophage intracellular parasitism, and these are controversial. Therefore, the present study aimed to evaluate the expression of inducible nitric oxide synthase (iNOS) in the lymph nodes and spleen of dogs affected by visceral leishmaniasis through immunohistochemistry and to determine its correlation with tissue parasite burden and serum interferon (IFN)-γ levels. Twenty-eight dogs were selected and assigned to one of two groups, symptomatic (n = 18) and asymptomatic (n = 10), according to clinical status and laboratory evaluation. A negative control group (n = 6) from a non-endemic region for visceral leishmaniasis was included as well. Parasite density (amastigotes/mm2) was similar between clinical groups in the lymph nodes (P = 0.2401) and spleen (P = 0.8869). The density of iNOS⁺ cells was higher in infected dogs compared to controls (P spleen (P = 0.5940) densities between symptomatic and asymptomatic dogs. A positive correlation was found between the number of iNOS⁺ cells in lymph nodes and interferon-γ levels (r = 0.3776; P = 0.0303), and there was a negative correlation between parasites and iNOS⁺ cell densities both in lymph nodes (r = -0.5341; P = 0.0034) and spleen (r = -0.4669; P = 0.0329). The negative correlation observed between tissue parasitism and the expression of iNOS may be a reflection of NO acting on the control of parasites.

  2. Total lymphoid irradiation of intractable rheumatoid arthritis

    International Nuclear Information System (INIS)

    Herbst, M.; Fritz, H.; Sauer, R.

    1986-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with fractionated total lymphoid irradiation, (total dose 20 Gy). Lasting improvement in clinical symptoms was found in four patients during treatment and the remaining patients experienced similar benefit within 2 months of irradiation. There was marked reduction in exacerbations and number of joints involved. Morning stiffness, joint swelling and tenderness decreased. Complications included severe fatigue during treatment and acute bacterial arthritis in multiple joints in one patient. Four patients have since died, one of renal failure, another of cardiogenic shock following surgery 3 and 24 months after total lymphoid irradiation. Both had generalised amyloidosis. The third patient developed joint empyema and died of toxic cardiac failure. The fourth died 3 months after resection of a Kaposi's sarcoma complicated by wound infection which responded to treatment. Immunologically, total lymphoid irradiation resulted in suppression of the absolute lymphocyte count and reduction in T-helper cells, the number of T-suppressor cells remaining unchanged. These data provide evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis. Total lymphoid irradiation can induce sustained improvement in clinical disease activity, but severe, possibly fatal, side-effects cannot be ignored. (author)

  3. Total lymphoid irradiation of intractable rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Herbst, M.; Fritz, H.; Sauer, R.

    1986-12-01

    Eleven patients with intractable rheumatoid arthritis were treated with fractionated total lymphoid irradiation, (total dose 20 Gy). Lasting improvement in clinical symptoms was found in four patients during treatment and the remaining patients experienced similar benefit within 2 months of irradiation. There was marked reduction in exacerbations and number of joints involved. Morning stiffness, joint swelling and tenderness decreased. Complications included severe fatigue during treatment and acute bacterial arthritis in multiple joints in one patient. Four patients have since died, one of renal failure, another of cardiogenic shock following surgery 3 and 24 months after total lymphoid irradiation. Both had generalised amyloidosis. The third patient developed joint empyema and died of toxic cardiac failure. The fourth died 3 months after resection of a Kaposi's sarcoma complicated by wound infection which responded to treatment. Immunologically, total lymphoid irradiation resulted in suppression of the absolute lymphocyte count and reduction in T-helper cells, the number of T-suppressor cells remaining unchanged. These data provide evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis. Total lymphoid irradiation can induce sustained improvement in clinical disease activity, but severe, possibly fatal, side-effects cannot be ignored.

  4. Bioengineering of artificial lymphoid organs

    OpenAIRE

    NOSENKO M.A.; DRUTSKAYA M.S.; MOISENOVICH M.M.; NEDOSPASOV S.A.

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cy...

  5. Bioengineering of Artificial Lymphoid Organs.

    Science.gov (United States)

    Nosenko, M A; Drutskaya, M S; Moisenovich, M M; Nedospasov, S A

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cytokine signaling pathways regulating these processes. We describe various polymeric materials, as scaffolds, for artificial tissue engineering. Finally, published studies in which artificial lymphoid organs were generated are reviewed and possible future directions in the field are discussed.

  6. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

    2015-01-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

  7. Exposure to non-ionizing electromagnetic fields emitted from mobile phones induced DNA damage in human ear canal hair follicle cells.

    Science.gov (United States)

    Akdag, Mehmet; Dasdag, Suleyman; Canturk, Fazile; Akdag, Mehmet Zulkuf

    2018-01-01

    The aim of this study was to investigate effect of radiofrequency radiation (RFR) emitted from mobile phones on DNA damage in follicle cells of hair in the ear canal. The study was carried out on 56 men (age range: 30-60 years old)in four treatment groups with n = 14 in each group. The groups were defined as follows: people who did not use a mobile phone (Control), people use mobile phones for 0-30 min/day (second group), people use mobile phones for 30-60 min/day (third group) and people use mobile phones for more than 60 min/day (fourth group). Ear canal hair follicle cells taken from the subjects were analyzed by the Comet Assay to determine DNA damages. The Comet Assay parameters measured were head length, tail length, comet length, percentage of head DNA, tail DNA percentage, tail moment, and Olive tail moment. Results of the study showed that DNA damage indicators were higher in the RFR exposure groups than in the control subjects. In addition, DNA damage increased with the daily duration of exposure. In conclusion, RFR emitted from mobile phones has a potential to produce DNA damage in follicle cells of hair in the ear canal. Therefore, mobile phone users have to pay more attention when using wireless phones.

  8. T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation. | Center for Cancer Research

    Science.gov (United States)

    The process by which self-reactive CD4+ T cells infiltrate the central nervous system (CNS) and trigger neuroinflammation is not fully understood. Lazarevic and colleagues show that NKp46+innate lymphoid cells dependent on the transcription factor T-bet are critical mediators in facilitating the entry of autoreactive CD4+ cells of the TH17 subset of helper T cells into the

  9. Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

    Science.gov (United States)

    Rigas, Diamanda; Lewis, Gavin; Aron, Jennifer L; Wang, Bowen; Banie, Homayon; Sankaranarayanan, Ishwarya; Galle-Treger, Lauriane; Maazi, Hadi; Lo, Richard; Freeman, Gordon J; Sharpe, Arlene H; Soroosh, Pejman; Akbari, Omid

    2017-05-01

    Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function. ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity. We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model. These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Why Innate Lymphoid Cells?

    Science.gov (United States)

    Kotas, Maya E; Locksley, Richard M

    2018-06-19

    Innate lymphoid cells (ILCs) are positioned in tissues perinatally, constitutively express receptors responsive to their organ microenvironments, and perform an arsenal of effector functions that overlap those of adaptive CD4 + T cells. Based on knowledge regarding subsets of invariant-like lymphocytes (e.g., natural killer T [NKT] cells, γδ T cells, mucosal-associated invariant T [MAIT] cells, etc.) and fetally derived macrophages, we hypothesize that immune cells established during the perinatal period-including, but not limited to, ILCs-serve intimate roles in tissue that go beyond classical understanding of the immune system in microbial host defense. In this Perspective, we propose mechanisms by which the establishment of ILCs and the tissue lymphoid niche during early development may have consequences much later in life. Although definitive answers require better tools, efforts to achieve deeper understanding of ILC biology across the mammalian lifespan have the potential to lift the veil on the unknown breadth of immune cell functions. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Tertiary lymphoid organs in Takayasu Arteritis

    Directory of Open Access Journals (Sweden)

    Marc eClement

    2016-04-01

    Full Text Available Objective: The role of B cells in the pathogenesis of Takayasu arteritis (TA is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs in the aortic wall of TA patients.Methods: Hematoxylin and eosin–stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20, follicular dendritic cells (FDCs, CD21, and high endothelial venules (HEVs, PNAd was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment and follow up data were extracted from medical records.Results: Aorta specimens from Bentall procedures were available from 7 patients (five female, aged 22 to 57 years with TA. Surgical treatment was performed at TA diagnosis (n=4 or at a median of 108 months [84-156] after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient.. Of note, ectopic follicles containing CD21+ FDCs were found in all patients (4/4 with increased aortic FDG uptake before surgery but were absent in all but one patients (2/3 with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center–like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells.Conclusion: Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

  12. Tertiary Lymphoid Organs in Takayasu Arteritis.

    Science.gov (United States)

    Clement, Marc; Galy, Adrien; Bruneval, Patrick; Morvan, Marion; Hyafil, Fabien; Benali, Khadija; Pasi, Nicoletta; Deschamps, Lydia; Pellenc, Quentin; Papo, Thomas; Nicoletti, Antonino; Sacre, Karim

    2016-01-01

    The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment, and follow-up data were extracted from medical records. Aorta specimens from Bentall procedures were available from seven patients (5 females, aged 22-57 years) with TA. Surgical treatment was performed at TA diagnosis (n = 4) or at a median of 108 months (84-156) after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient. Of note, ectopic follicles containing CD21(+) FDCs were found in all patients (4/4) with increased aortic (18)F-fluoro-deoxyglucose (FDG) uptake before surgery but were absent in all but one patients (2/3) with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center-like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells. Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

  13. Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Joselli S Silva

    Full Text Available Visceral leishmaniasis is associated with atrophy and histological disorganization of splenic compartments. In this paper, we compared organized and disorganized splenic lymphoid tissue from dogs naturally infected with Leishmania infantum assessing the size of the white pulp compartments, the distribution of T, B and S100+ dendritic cells, using immunohistochemistry and morphometry and the expression of CCR7 and the cytokines, CXCL13, lymphotoxin (LT-α, LT-β, CCL19, CCL21, TNF-α, IL-10, IFN-γ and TGF-β, using by real time RT-PCR. The lymphoid follicles and marginal zones were smaller (3.2 and 1.9 times, respectively; Mann-Whitney, P<0.02 in animals with disorganized splenic tissue in comparison to those with organized splenic lymphoid tissue. In spleens with disorganized lymphoid tissue, the numbers of T cells and S100+ dendritic cells were decreased in the follicles, and the numbers of B cells were reduced in both the follicles and marginal zones. CXCL13 mRNA expression was lower in animals with disorganized lymphoid tissue (0.5±0.4 compared to those with organized lymphoid tissue (2.7±2.9, both relative to 18S expression, P = 0.01. These changes in the spleen were associated with higher frequency of severe disease (7/12 in the animals with disorganized than in animals with organized (2/13, Chi-square, P = 0.01 splenic lymphoid tissue. The data presented herein suggest that natural infection with Leishmania infantum is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis. Furthermore the fact that this work uses dogs naturally infected with Leishmania infantum emphasizes the relevance of the data presented herein for the knowledge on the canine and human visceral leishmaniasis.

  14. The physiology of follicle selection

    Directory of Open Access Journals (Sweden)

    Zeleznik Anthony J

    2004-06-01

    Full Text Available Abstract During the follicular phase of the primate menstrual cycle, a single follicle usually matures to the preovulatory stage and releases its oocyte for fertilization and the potential establishment of pregnancy. In assisted reproductive technology procedures, it is desirable to override the natural process of follicle selection to produce many oocytes that are capable of being fertilized and undergoing normal embryo development. The goal of this chapter is to summarize the current views regarding the natural process of follicle selection in primates and to discuss how this process may be amplified to produce a greater number of oocytes.

  15. PU.1 is essential for CD11c expression in CD8(+/CD8(- lymphoid and monocyte-derived dendritic cells during GM-CSF or FLT3L-induced differentiation.

    Directory of Open Access Journals (Sweden)

    Xue-Jun Zhu

    Full Text Available Dendritic cells (DCs regulate innate and acquired immunity through their roles as antigen-presenting cells. Specific subsets of mature DCs, including monocyte-derived and lymphoid-derived DCs, can be distinguished based on distinct immunophenotypes and functional properties. The leukocyte integrin, CD11c, is considered a specific marker for DCs and it is expressed by all DC subsets. We created a strain of mice in which DCs and their progenitors could be lineage traced based on activity of the CD11c proximal promoter. Surprisingly, we observed levels of CD11c promoter activity that were similar in DCs and in other mature leukocytes, including monocytes, granulocytes, and lymphocytes. We sought to identify DNA elements and transcription factors that regulate DC-associated expression of CD11c. The ets transcription factor, PU.1, is a key regulator of DC development, and expression of PU.1 varies in different DC subsets. GM-CSF increased monocyte-derived DCs in mice and from mouse bone marrow cultured in vitro, but it did not increase CD8(+ lymphoid-derived DCs or B220(+ plasmacytoid DCs. FLT3L increased both monocyte-derived DCs and lymphoid-derived DCs from mouse bone marrow cultured in vitro. GM-CSF increased the 5.3 Kb CD11c proximal promoter activity in monocyte-derived DCs and CD8(+ lymphoid-derived DCs, but not in B220(+ plasmacytoid DCs. In contrast, FLT3L increased the CD11c proximal promoter activity in both monocyte-derived DCs and B220(+ plasmacytoid DCs. We used shRNA gene knockdown and chromatin immunoprecipitation to demonstrate that PU.1 is required for the effects of GM-CSF or FLT3L on monocyte-derived DCs. We conclude that both GM-CSF and FLT3L act through PU.1 to activate the 5.3 Kb CD11c proximal promoter in DCs and to induce differentiation of monocyte-derived DCs. We also confirm that the CD11c proximal promoter is not sufficient to direct lineage specificity of CD11c expression, and that additional DNA elements are required

  16. Role of the gut-associated and secondary lymphoid tissue in the induction of chronic colitis.

    Science.gov (United States)

    Takebayashi, Koichi; Koboziev, Iurii; Ostanin, Dmitry V; Gray, Laura; Karlsson, Fridrik; Robinson-Jackson, Sherry A; Kosloski-Davidson, Melissa; Dooley, Angela Burrows; Zhang, Songlin; Grisham, Matthew B

    2011-01-01

    It is well known that enteric bacterial antigens drive the development of chronic colitis in a variety of different mouse models of the inflammatory bowel diseases (IBD). The objective of this study was to evaluate the role of gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes (MLNs) and spleen in the pathogenesis of chronic colitis in mice. Surgical as well as genetic approaches were used to generate lymphopenic mice devoid of one or more of these lymphoid tissues. For the first series of studies, we subjected recombinase activating gene-1-deficient mice (RAG(-/-) ) to sham surgery (Sham), mesenteric lymphadenectomy (MLNx), splenectomy (Splx) or both (MLNx/Splx). In a second series of studies we intercrossed lymphotoxinβ-deficient (LTβ(-/-) ) mice with RAG(-/-) animals to generate LTβ(-/-) x RAG(-/-) offspring that were anticipated to contain functional MLNs but be devoid of GALT and most peripheral lymph nodes. Flow purified naïve (CD4(+) CD45RB(high) ) T-cells were adoptively transferred into the different groups of RAG(-/-) recipients to induce chronic colitis. We found that at 3-5 wks following T-cell transfer, all four of the surgically-manipulated RAG(-/-) groups (Sham, MLNx, Splx and MLNx/Splx) developed chronic colitis that was similar in onset and severity. Flow cytometric analysis revealed no differences among the different groups with respect to surface expression of different gut-homing markers nor were there any differences noted in IFN-γ and IL-17 generation by mononuclear cells isolated among these surgically-manipulated mice. Although we anticipated that LTβ(-/-) x RAG(-/-) mice would contain functional MLNs but be devoid of GALT and peripheral lymph nodes (PLNs), we found that LTβ(-/-) x RAG(-/-) mice were in fact devoid of MLNs as well as GALT and PLNs. Adoptive transfer of CD45RB(high) T-cells into LTβ(-/-) x RAG(-/-) mice or their littermate controls (LTβ(+/+) x RAG

  17. The B-Cell Follicle in HIV Infection: Barrier to a Cure.

    Science.gov (United States)

    Bronnimann, Matthew P; Skinner, Pamela J; Connick, Elizabeth

    2018-01-01

    The majority of HIV replication occurs in secondary lymphoid organs (SLOs) such as the spleen, lymph nodes, and gut-associated lymphoid tissue. Within SLOs, HIV RNA + cells are concentrated in the B-cell follicle during chronic untreated infection, and emerging data suggest that they are a major source of replication in treated disease as well. The concentration of HIV RNA + cells in the B-cell follicle is mediated by several factors. Follicular CD4 + T-cell subsets including T-follicular helper cells and T-follicular regulatory cells are significantly more permissive to HIV than extrafollicular subsets. The B cell follicle also contains a large reservoir of extracellular HIV virions, which accumulate on the surface of follicular dendritic cells (FDCs) in germinal centers. FDC-bound HIV virions remain infectious even in the presence of neutralizing antibodies and can persist for months or even years. Moreover, the B-cell follicle is semi-immune privileged from CTL control. Frequencies of HIV- and SIV-specific CTL are lower in B-cell follicles compared to extrafollicular regions as the majority of CTL do not express the follicular homing receptor CXCR5. Additionally, CTL in the B-cell follicle may be less functional than extrafollicular CTL as many exhibit the recently described CD8 T follicular regulatory phenotype. Other factors may also contribute to the follicular concentration of HIV RNA + cells. Notably, the contribution of NK cells and γδ T cells to control and/or persistence of HIV RNA + cells in secondary lymphoid tissue remains poorly characterized. As HIV research moves increasingly toward the development of cure strategies, a greater understanding of the barriers to control of HIV infection in B-cell follicles is critical. Although no strategy has as of yet proven to be effective, a range of novel therapies to address these barriers are currently being investigated including genetically engineered CTL or chimeric antigen receptor T cells that express

  18. The B-Cell Follicle in HIV Infection: Barrier to a Cure

    Directory of Open Access Journals (Sweden)

    Matthew P. Bronnimann

    2018-01-01

    Full Text Available The majority of HIV replication occurs in secondary lymphoid organs (SLOs such as the spleen, lymph nodes, and gut-associated lymphoid tissue. Within SLOs, HIV RNA+ cells are concentrated in the B-cell follicle during chronic untreated infection, and emerging data suggest that they are a major source of replication in treated disease as well. The concentration of HIV RNA+ cells in the B-cell follicle is mediated by several factors. Follicular CD4+ T-cell subsets including T-follicular helper cells and T-follicular regulatory cells are significantly more permissive to HIV than extrafollicular subsets. The B cell follicle also contains a large reservoir of extracellular HIV virions, which accumulate on the surface of follicular dendritic cells (FDCs in germinal centers. FDC-bound HIV virions remain infectious even in the presence of neutralizing antibodies and can persist for months or even years. Moreover, the B-cell follicle is semi-immune privileged from CTL control. Frequencies of HIV- and SIV-specific CTL are lower in B-cell follicles compared to extrafollicular regions as the majority of CTL do not express the follicular homing receptor CXCR5. Additionally, CTL in the B-cell follicle may be less functional than extrafollicular CTL as many exhibit the recently described CD8 T follicular regulatory phenotype. Other factors may also contribute to the follicular concentration of HIV RNA+ cells. Notably, the contribution of NK cells and γδ T cells to control and/or persistence of HIV RNA+ cells in secondary lymphoid tissue remains poorly characterized. As HIV research moves increasingly toward the development of cure strategies, a greater understanding of the barriers to control of HIV infection in B-cell follicles is critical. Although no strategy has as of yet proven to be effective, a range of novel therapies to address these barriers are currently being investigated including genetically engineered CTL or chimeric antigen receptor T cells

  19. Lymphoid Tissue Grafts in Man

    Energy Technology Data Exchange (ETDEWEB)

    Kay, H. E.M. [Royal Marsden Hospital, Institute of Cancer Research, London (United Kingdom)

    1969-07-15

    Grafts of lymphoid tissue or of lymphoid stem cells may be appropriate in the treatment of some congenital immune deficiency disorders. The reasons for preferring tissues of foetal origin are discussed and the evidence for foetal immunocompetence is briefly summarized. Methods of storing foetal liver cells and cells or fragments of thymus are mentioned, and the organization of the Foetal Tissue Bank of the Royal Marsden Hospital is described. Clinical data from transplantation of lymphoid cells in various immune deficiency disorders are briefly presented. (author)

  20. The potential of follicle-stimulating hormone peptide-modified triptolide-loaded nanoparticles to induce a mouse model of premature ovarian insufficiency

    Directory of Open Access Journals (Sweden)

    Chen XY

    2015-04-01

    Full Text Available Xiu-Ying Chen,1–3 Wu-Lian Chen,4 Min Ma,1–3 Chao Gu,1,2 Xi-Rong Xiao,1,2 Bin Li1,2 1Obstetrics and Gynecology Hospital, Fudan University, 2Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 3Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 4State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People’s Republic of ChinaAbstract: The use of triptolide (TP is limited by its poor water solubility and severe toxicity. In this study, we developed an active drug delivery system (TP-loaded nanoparticles that could help improve the water solubility of TP and decrease its toxicity. Then, we investigated whether TP-loaded nanoparticles could be used to establish a novel premature ovarian insufficiency mouse model. The mice treated with TP-loaded nanoparticles for 35 days displayed normal growth, decreased serum antimullerian hormone, prominent ovarian fibrosis and vacuolar changes, fewer follicles and corpus lutea, increased collapsed oocytes and follicle apoptosis, and sterility. In conclusion, this model appears to show the reproductive characteristics associated with premature ovarian insufficiency in women and will allow us to study the mechanism of the effects of traditional Chinese medicine on gonadal toxicity. Keywords: peptide, nanoparticles, drug delivery, premature ovarian insufficiency, animal model

  1. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    International Nuclear Information System (INIS)

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-01-01

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  2. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  3. Twin Rectal Tonsils Mimicking Carcinoid or Mucosa-Associated Lymphoid Tissue Lymphoma.

    Science.gov (United States)

    Takehara, Masanori; Muguruma, Naoki; Kitamura, Shinji; Kimura, Tetsuo; Okamoto, Koichi; Miyamoto, Hiroshi; Bando, Yoshimi; Takayama, Tetsuji

    2017-09-01

    The rectal tonsil is a rare polypoid lesion exclusively found in the rectum and is considered a reactive proliferation of the lymphoid tissue. Although this lesion is benign, we recommend that it should be differentiated from carcinoid or polypoid type of mucosa-associated lymphoid tissue lymphomas, based on gross findings. In this case report, we describe a case of rectal lesions with a unique appearance in a 41-year-old man. Colonoscopy revealed two 5-mm-sized nodules located opposite from each other on the left and right sides of the lower rectum. Endoscopic mucosal resection was conducted. Histopathologically, both lesions were mainly located in the submucosa and consisted of prominent lymphoid follicles with germinal centers of various sizes. No immunoreactivity of Bcl-2 was seen in the germinal centers. Immunohistochemical staining for kappa and lambda light chains revealed a polyclonal pattern. Therefore, these lesions were diagnosed as rectal tonsils.

  4. Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation.

    Science.gov (United States)

    Koboziev, Iurii; Karlsson, Fridrik; Grisham, Matthew B

    2010-10-01

    The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. © 2010 New York Academy of Sciences.

  5. Characteristic of innate lymphoid cells (ILC

    Directory of Open Access Journals (Sweden)

    Mateusz Adamiak

    2014-12-01

    Full Text Available Innate lymphoid cells (ILC is a newly described family of immune cells that are part of the natural immunity which is important not only during infections caused by microorganisms, but also in the formation of lymphoid tissue, tissue remodeling after damage due to injury and homeostasis tissue stromal cells. Family ILC cells form NK cells (natural killer and lymphoid tissue inducer T cells (LTi, which, although they have different functions, are evolutionarily related. NK cells are producing mainly IFN-γ, whereas LTi cells as NKR+LTi like, IL-17 and/or IL-22, which suggests that the last two cells, can also represent the innate versions of helper T cell - TH17 and TH22. Third population of ILC is formed by cells with characteristics such as NK cells and LTi (ILC22 - which are named NK22 cells, natural cytotoxicity receptor 22 (NCR22 cells or NK receptor-positive (LTi NKR+ LTi cells. Fourth population of ILC cells are ILC17 - producing IL-17, while the fifth is formed by natural helper type 2 T cells (nTH2, nuocyte, innate type 2 helper cells (IH2 and multi-potent progenitor type 2 cells (MPPtype2. Cells of the last population synthesize IL-5 and IL-13. It is assumed that an extraordinary functional diversity of ILC family, resembles T cells, probably because they are under the control of the corresponding transcription factors - as direct regulation factors, such as the family of lymphocytes T.

  6. Androgen Stimulates Growth of Mouse Preantral Follicles In Vitro: Interaction With Follicle-Stimulating Hormone and With Growth Factors of the TGFβ Superfamily.

    Science.gov (United States)

    Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Franks, Stephen; Hardy, Kate

    2017-04-01

    Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS.

  7. The amazing miniorgan: Hair follicle

    Directory of Open Access Journals (Sweden)

    Çiler Çelik Özenci

    2014-06-01

    Full Text Available Hair is a primary characteristic of mammals, and exerts a wide range of functions including thermoregulation, physical protection, sensory activity, and social interactions. The hair shaft consists of terminally differentiated keratinocytes that are produced by the hair follicle. Hair follicle development takes place during fetal skin development and relies on tightly regulated ectodermal–mesodermal interactions. Hair follicles form during embryonic development and, after birth, undergo recurrent cycling of growth (anagen, apoptosis-driven regression (catagen, and relative quiescence (telogen. As a functional mini-organ, the hair follicle develops in an environment with dynamic and alternating changes of diverse molecular signals. Our molecular understanding of hair follicle biology relies heavily on genetically engineered mouse models with abnormalities in hair structure, growth, and/or pigmentation and significant advances have been made toward the identification of key signaling pathways and the regulatory genes involved. In this review, the basic concepts of hair follicle, a mini-complex organ, biology will be presented and its importance in clinical applications will be summarized.

  8. Clusterin in human gut-associated lymphoid tissue, tonsils, and adenoids: localization to M cells and follicular dendritic cells.

    Science.gov (United States)

    Verbrugghe, Phebe; Kujala, Pekka; Waelput, Wim; Peters, Peter J; Cuvelier, Claude A

    2008-03-01

    The follicle-associated epithelium (FAE) overlying the follicles of mucosa-associated lymphoid tissue is a key player in the initiation of mucosal immune responses. We recently reported strong clusterin expression in the FAE of murine Peyer's patches. In this study, we examined the expression of clusterin in the human gut-associated lymphoid tissue (GALT) and Waldeyer's ring. Immunohistochemistry for clusterin in human Peyer's patches, appendix and colon lymphoid follicles revealed expression in M cells and in follicular dendritic cells (FDCs). Using cryo-immunogold electron microscopy in Peyer's patches, we observed cytosolic immunoreactivity in M cells and labeling in the ER/Golgi biosynthetic pathway in FDCs. In palatine tonsils and adenoids, we demonstrated clusterin expression in germinal centers and in the lymphoepithelium in the crypts where M cells are localized. In conclusion, clusterin is expressed in M cells and follicular dendritic cells at inductive sites of human mucosa-associated lymphoid tissue suggesting a role for this protein in innate immune responses. Moreover, the use of clusterin as a human M cell marker could prove to be a valuable tool in future M cell research.

  9. Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

    Science.gov (United States)

    Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen

    2017-02-14

    Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 + group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 + ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 + ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 - cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 + ILC3s. NRP1 + ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling

    NARCIS (Netherlands)

    Spits, Hergen; Di Santo, James P.

    2011-01-01

    Research has identified what can be considered a family of innate lymphoid cells (ILCs) that includes not only natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells but also cells that produce interleukin 5 (IL-5), IL-13, IL-17 and/or IL-22. These ILC subsets are developmentally related,

  11. Resveratrol supplementation rescues pool of growing follicles and ovarian stroma from Cisplatin-induced toxicity on the ovary in Sprague-Dawley rats: An experimental study

    Directory of Open Access Journals (Sweden)

    Gbotolorun Stella Chinwe

    2018-02-01

    Full Text Available Background: Cisplatin is a potent antineoplastic agent for many cancers but causes several levels of gonadal damage. Ovarian toxicity is a major concern of young cancer patients undergoing chemotherapy. Objective: This study sought to examine the effect of Cisplatin and Resveratrol supplementation on ovarian function in Sprague-Dawley rats. Materials and Methods: In this experimental study, 45 cyclic Sprague-Dawley rats with an average weight of 160 gr were divided into 9 groups (n=5/group. Group 1 was used as control and received distilled water. Groups 2 and 9 received Cisplatin only. Groups 3, 4, and 5 received different doses of Resveratrol after a single dose of Cisplatin. Groups 6, 7, and 8 received Resveratrol before Cisplatin. At sacrifice, the ovary was analyzed for histopathology, biochemical indices of oxidation and hormonal assay. Results: Relative and absolute organ weights were notably increased (p=0.001, 0.01 in the prophylactic groups relative to the groups that received Resveratrol after Cisplatin. Also, glutathione, superoxide dismutase and catalase were significantly increased (p=0.047, 0.01, 0.023 in a dose-dependent manner when compared to Cisplatin group only. Malondialdehyde decreased significantly (p=0.001 in the groups that received high dose Resveratrol compared with the control and Cisplatin alone groups. Although oestrogen showed no significant difference within the groups (p=0.48, Resveratrol significantly increased progesterone, follicle stimulating hormone and luteinizing hormone levels (p=0.007, 0.001, 0.006 at high doses when compared with Cisplatin alone groups. Ovarian histoarchitecture was best preserved in the prophylactic groups in a dose-dependent manner. Conclusion: Resveratrol supplementation confers protection and preserves ovarian follicles from Cisplatin toxicity in Sprague-Dawley rats.

  12. Induction and Analysis of Bronchus-Associated Lymphoid Tissue.

    Science.gov (United States)

    Fleige, Henrike; Förster, Reinhold

    2017-01-01

    Bronchus-associated lymphoid tissue (BALT) forms spontaneously in the lung after pulmonary infection and has been identified as a highly organized lymphoid structure supporting the efficient priming of T cells in the lung. To explore the mechanisms and instructive signals controlling BALT neogenesis we used both, a single dose of vaccinia virus MVA and repeated inhalations of heat-inactivated Pseudomonas aeruginosa (P. aeruginosa). Intranasal administration of both pathogens induces highly organized BALT but distinct pathways and molecules are used to promote the development of BALT. Here, we describe the induction and phenotype of the distinct types of BALT as well as the immunofluorescence microscopy-based analysis of the induced lymphoid tissue in the lung.

  13. Prions and lymphoid organs

    Science.gov (United States)

    O’Connor, Tracy; Aguzzi, Adriano

    2013-01-01

    Prion colonization of secondary lymphoid organs (SLOs) is a critical step preceding neuroinvasion in prion pathogenesis. Follicular dendritic cells (FDCs), which depend on both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance, are thought to be the primary sites of prion accumulation in SLOs. However, prion titers in RML-infected TNFR1−/− lymph nodes and rates of neuroinvasion in TNFR1−/− mice remain high despite the absence of mature FDCs. Recently, we discovered that TNFR1-independent prion accumulation in lymph nodes relies on LTβR signaling. Loss of LTβR signaling in TNFR1−/− lymph nodes coincided with the de-differentiation of high endothelial venules (HEVs)—the primary sites of lymphocyte entry into lymph nodes. These findings suggest that HEVs are the sites through which prions initially invade lymph nodes from the bloodstream. Identification of HEVs as entry portals for prions clarifies a number of previous observations concerning peripheral prion pathogenesis. However, a number of questions still remain: What is the mechanism by which prions are taken up by HEVs? Which cells are responsible for delivering prions to lymph nodes? Are HEVs the main entry site for prions into lymph nodes or do alternative routes also exist? These questions and others are considered in this article. PMID:23357827

  14. Total lymphoid irradiation

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    An outline review notes recent work on total lymphoid irradiation (TLI) as a means of preparing patients for grafts and particularly for bone-marrow transplantation. T.L.I. has proved immunosuppressive in rats, mice, dogs, monkeys and baboons; when given before bone-marrow transplantation, engraftment took place without, or with delayed rejection or graft-versus-host disease. Work with mice has indicated that the thymus needs to be included within the irradiation field, since screening of the thymus reduced skin-graft survival from 50 to 18 days, though irradiation of the thymus alone has proved ineffective. A more lasting tolerance has been observed when T.L.I. is followed by an injection of donor bone marrow. 50% of mice treated in this way accepted allogenic skin grafts for more than 100 days, the animals proving to be stable chimeras with 50% of their peripheral blood lymphocytes being of donor origin. Experiments of a similar nature with dogs and baboons were not so successful. (U.K.)

  15. Role of lymphotoxin and homeostatic chemokines in the development and function of local lymphoid tissues in the respiratory tract.

    Science.gov (United States)

    Rangel-Moreno, Javier; Carragher, Damian; Randall, Troy D

    2007-01-01

    Secondary lymphoid organs are strategically placed to recruit locally activated antigen presenting cells (APCs) as well as naïve, recirculating T and B cells. The structure of secondary lymphoid organs - separated B and T zones, populations of specialized stromal cells, high endothelial venules and lymphatic vessles - has also evolved to maximize encounters between APCs and lymphocytes and to facilitate the expansion and differentiation of antigen-stimulated T and B cells. Many of the general mechanisms that govern the development and organization of secondary lymphoid organs have been identified over the last decade. However, the specific cellular and molecular interactions involved in the development and organization of each secondary lymphoid organ are slightly different and probably reflect the cell types available at that time and location. Here we review the mechanisms involved in the development, organization and function of local lymphoid tissues in the respiratory tract, including Nasal Associated Lymphoid Tissue (NALT) and inducible Bronchus Associated Lymphoid Tissue (iBALT).

  16. Total lymphoid irradiation in rhesus monkeys

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Maat, B.; Hogeweg, B.

    Total lymphoid irradiation (TLI) consists of three contiguous fields, a mantle, an inverted Y and a spleen field. TLI induces a state of immunosuppression in patients with Hodgkin disease or in small rodents. Infusion of allogeneic bone marrow cells into mice after TLI led to the development split haemopoietic chimerism and indefinite survival of skin grafts from the bone marrow donor. A protocol for TLI was developed for rhesus monkeys to attempt to verify these interesting observations in a pre-clinical animal model. (Auth.)

  17. Nasal associated lymphoid tissue of the Syrian golden hamster expresses high levels of PrPC.

    Directory of Open Access Journals (Sweden)

    Melissa D Clouse

    Full Text Available The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc comes into contact with native prion protein (PrPC and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.

  18. Nasal associated lymphoid tissue of the Syrian golden hamster expresses high levels of PrPC.

    Science.gov (United States)

    Clouse, Melissa D; Shikiya, Ronald A; Bartz, Jason C; Kincaid, Anthony E

    2015-01-01

    The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc) comes into contact with native prion protein (PrPC) and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.

  19. High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

    Science.gov (United States)

    Ager, Ann

    2017-01-01

    The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

  20. Effect of different culture systems and 3, 5, 3'-triiodothyronine/follicle-stimulating hormone on preantral follicle development in mice.

    Directory of Open Access Journals (Sweden)

    Cheng Zhang

    Full Text Available The mechanical method to isolate preantral follicle has been reported for many years. However, the culture systems in vitro are still unstable. The aim of this study was to analyze the effect of the culture system of mice preantral follicles on the follicular development in vitro. The results showed that the 96-well plate system was the most effective method for mice follicle development in vitro (volume change: 51.71%; survival rate: 89%, at day 4. Follicle-stimulating hormone (FSH and Thyroid hormone (TH are important for normal follicular development and dysregulation of hormones are related with impaired follicular development. To determine the effect of hormone on preantral follicular development, we cultured follicle with hormones in the 96-well plate culture system and found that FSH significantly increased preantral follicular growth on day 4. The FSH-induced growth action was markedly enhanced by T₃ although T₃ was ineffective alone. We also demonstrated by QRT-PCR that T₃ significantly enhanced FSH-induced up-regulation of Xiap mRNA level. Meanwhile, Bad, cell death inducer, was markedly down-regulated by the combination of hormones. Moreover, QRT-PCR results were also consistent with protein regulation which detected by Western Blotting analysis. Taken together, the findings of the present study demonstrate that 96-well plate system is an effective method for preantral follicle development in vitro. Moreover, these results provide insights on the role of thyroid hormone in increasing FSH-induced preantral follicular development, which mediated by up-regulating Xiap and down-regulating Bad.

  1. Interactions between the intestinal microbiota and innate lymphoid cells

    Science.gov (United States)

    Chen, Vincent L; Kasper, Dennis L

    2014-01-01

    The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells. PMID:24418741

  2. Induction of secondary and tertiary lymphoid structures in the skin.

    NARCIS (Netherlands)

    Cupedo, T.; Jansen, W.; Kraal, G.; Mebius, R.E.

    2004-01-01

    During embryogenesis a developmental program leading to the formation of lymph nodes and Peyer's patches is initiated. We now show that lymph node-like structures as well as tertiary lymphoid structures can ectopically be induced by intradermal injection of newborn lymph node-derived cells.

  3. Follicle-stimulating hormone (FSH) blood test

    Science.gov (United States)

    ... ency/article/003710.htm Follicle-stimulating hormone (FSH) blood test To use the sharing features on this page, please enable JavaScript. The follicle stimulating hormone (FSH) blood test measures the level of FSH in blood. FSH ...

  4. Innate lymphoid cells and the skin

    OpenAIRE

    Salimi, Maryam; Ogg, Graham

    2014-01-01

    Innate lymphoid cells are an emerging family of effector cells that contribute to lymphoid organogenesis, metabolism, tissue remodelling and protection against infections. They maintain homeostatic immunity at barrier surfaces such as lung, skin and gut (Nature 464:1367?1371, 2010, Nat Rev Immunol 13: 145?149, 2013). Several human and mouse studies suggest a role for innate lymphoid cells in inflammatory skin conditions including atopic eczema and psoriasis. Here we review the innate lymphoid...

  5. Florid reactive lymphoid hyperplasia of terminal ileum

    OpenAIRE

    Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

    2010-01-01

    Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn’s disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn’s disease. In florid lymphoid hyperplasia limited resection may b...

  6. Effect Of Crude Protein Levels And Follicle Stimulation On Egg ...

    African Journals Online (AJOL)

    Two groups received 16% crude protein (CP) level diets and the other two groups, 32%. One each of the two groups received follicle stimulation, induced by administration of Clomifene citrate (1.5mg/kg) via cathetered 5ml syringe through the 10week experimental period, with feed and water offered ad libitum.

  7. Ratchet effect for nanoparticle transport in hair follicles.

    Science.gov (United States)

    Radtke, Matthias; Patzelt, Alexa; Knorr, Fanny; Lademann, Jürgen; Netz, Roland R

    2017-07-01

    The motion of a single rigid nanoparticle inside a hair follicle is investigated by means of Brownian dynamics simulations. The cuticular hair structure is modeled as a periodic asymmetric ratchet-shaped surface. Induced by oscillating radial hair motion we find directed nanoparticle transport into the hair follicle with maximal velocity at a specific optimal frequency and an optimal particle size. We observe flow reversal when switching from radial to axial oscillatory hair motion. We also study the diffusion behavior and find strongly enhanced diffusion for axial motion with a diffusivity significantly larger than for free diffusion. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Immunoregulatory changes induced by total lymphoid irradiation. II. Development of thymus-leukemia antigen-positive and -negative suppressor T cells that differ in their regulatory function

    International Nuclear Information System (INIS)

    King, D.P.; Strober, S.

    1981-01-01

    BALB/c mice treated with total lymphoid irradiation (TLI) develop non-antigen-specific suppressor cells of the adoptive secondary antibody response and of the mixed leukocyte reaction. Suppressors of the adoptive anti-DNP response were eliminated by incubation of spleen cells with anti-Thy-1.2 or anti-thymus-leukemia (TL) antiserum and complement before cell transfer. Thymectomy before TLI prevented the appearance of the latter suppressor cells. On the other hand, suppressors of the MLR were eliminated by incubation of spleen cells with anti-Thy-1.2 but not anti-TL antiserum and complement. Thymectomy before TLI did not prevent their subsequent development. Thus, two subpopulations of suppressor T cells that differ in the expression of the TL surface antigen, dependence on the presence of the thymus, and in regulatory functions develop after TLI. The TL+, thymus-dependent cell suppresses the adoptive antibody response, and the TL-, thymus-independent cell suppresses the MLR

  9. Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

    Science.gov (United States)

    Hirota, Keiji; Hashimoto, Motomu; Ito, Yoshinaga; Matsuura, Mayumi; Ito, Hiromu; Tanaka, Masao; Watanabe, Hitomi; Kondoh, Gen; Tanaka, Atsushi; Yasuda, Keiko; Kopf, Manfred; Potocnik, Alexandre J; Stockinger, Brigitta; Sakaguchi, Noriko; Sakaguchi, Shimon

    2018-06-19

    Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. DNMT3AR882H mutant and Tet2 inactivation cooperate in the deregulation of DNA methylation control to induce lymphoid malignancies in mice

    DEFF Research Database (Denmark)

    Scourzic, L; Couronné, L; Pedersen, Marianne Terndrup

    2016-01-01

    malignancies with one mouse developing an AITL-like disease, two mice presenting acute myeloid leukemia (AML)-like and two others T-cell acute lymphoblastic leukemia (T-ALL)-like diseases within 6 months following transplantation. Serial transplantations of DNMT3A(R882H) Tet2(-/-) progenitors led...... to a differentiation bias toward the T-cell compartment, eventually leading to AITL-like disease in 9/12 serially transplanted recipients. Expression profiling suggested that DNMT3A(R882H) Tet2(-/-) T-ALLs resemble those of NOTCH1 mutant. Methylation analysis of DNMT3A(R882H) Tet2(-/-) T-ALLs showed a global increase...... in DNA methylation affecting tumor suppressor genes and local hypomethylation affecting genes involved in the Notch pathway. Our data confirm the transformation potential of DNMT3A(R882H) Tet2(-/-) progenitors and represent the first cooperative model in mice involving Tet2 inactivation driving lymphoid...

  11. The Effects of Hydro-alcoholic Extract of Raspberry Fruit on Ovarian follicles and serum parameters in Poly Cystic Ovary Syndrome-Induced Rat

    Directory of Open Access Journals (Sweden)

    mohamad Nabiuni

    2015-02-01

    Full Text Available Background & aim: Polycystic Ovary Syndrome is an endocrine disorder leading to lack of ovulation and has inflammatory aspects. Raspberry extract, with possession of bioactive compounds such as Anthocyanins and polyphenols, have anti-inflammatory properties. In this study, the anti-inflammatory effects of raspberry extract on the development process of ovarian follicles and hormones level of pituitary, ovarian, and liver in rats suffering from PCOS were examined. Methods: In the present experimental study, 120 adult Wistar rats were divided into three groups of control, PCOS, and treated with raspberry. The induction of syndrome was done by 2mg Estradiol valerate. After a period of 60 days, 100, 150 and 200 mg/kg BW raspberry extract was injected intraperitoneally. Control group received no injection. Ten days after the last injection, all groups were anesthetized by chloroform and the serum and ovary of all groups were collected in order to investigate the histological and serologic changes. Data obtained were analyzed by using one-way ANOVA. Results: Raspberry-treated group showed a significant decrease in the hormones rate of testosterone, estradiol, LH, and CRP compared with PCOS (p<0.05, whereas a significant increase was observed in the serum level of Progesterone and FSH (p<0.05. A significant increase was observed in the number of corpus luteum and granulosa layer thickness in the raspberry-treated group compared with PCOS (p<0.05. Conclusion: The results demonstrated that the antioxidant and anti-inflammatory effects of raspberry extract was effective on regulating the hormones, CRPand improving of cysts which led to the initiation of ovulation.

  12. M cells and granular mononuclear cells in Peyer's patch domes of mice depleted of their lymphocytes by total lymphoid irradiation

    International Nuclear Information System (INIS)

    Ermak, T.H.; Steger, H.J.; Strober, S.; Owen, R.L.

    1989-01-01

    The cytoarchitecture of Peyer's patches that were depleted of their lymphocytes by total lymphoid irradiation (TLI) was examined with particular attention to the effects on M cells in the follicle epithelium and on mononuclear cells in follicle domes underlying the epithelium. Five-month-old, specific pathogen-free Balb/c mice were irradiated with 200-250 rad/day, five times a week to a total dose of 3400-4250, and their Peyer's patches were either fixed for electron microscopy or frozen for immunohistochemistry 1-4 days after completion of irradiation. Control mice were examined at the same time intervals. Follicle domes of TLI mice had approximately one fourth the epithelial surface area of domes of control mice. Within the epithelium, lymphoid cells were virtually depleted after TLI, and yet the epithelium contained M cells. In control mice, most M cells were accompanied by lymphoid cells in invaginations of the apical-lateral cell membrane. In TLI mice, most M cells did not have such apical-lateral invaginations and were columnar shaped. Other than lacking lymphocytes, these cells appeared to be mature M cells. Some M cells did have lymphoid cells or granular mononuclear cells below their basal membranes, adjacent to the basal lamina. Below the epithelium, the proportion of granular mononuclear cells was greatly increased following TLI. The retention of M cells and the increase in proportion of granular mononuclear cells in follicle domes are consistent with selective depletion of lymphocytes following TLI. Persistence of M cells without lymphocytic invaginations after TLI suggests that M cells can differentiate in the absence of, or at least in the presence of very few, lymphocytes, and that invagination by lymphocytes is not necessary to maintain mature M cell morphology

  13. Early initiation of highly active antiretroviral therapy fails to reverse immunovirological abnormalities in gut-associated lymphoid tissue induced by acute HIV infection.

    Science.gov (United States)

    Tincati, Camilla; Biasin, Mara; Bandera, Alessandra; Violin, Michela; Marchetti, Giulia; Piacentini, Luca; Vago, Gian Luca; Balotta, Claudia; Moroni, Mauro; Franzetti, Fabio; Clerici, Mario; Gori, Andrea

    2009-01-01

    During the acute phase of HIV infection, large CD4+ T-cell depletion occurs in the gastrointestinal tract. The kinetics of CD4+ T-cell decrease and highly active antiretroviral therapy (HAART)-mediated immune reconstitution were evaluated. Rectosigmoid colonic (RSC) biopsies and blood samples of nine patients with acute HIV infection were collected. CD4+ T-cell count, HIV RNA, intracellular HIV DNA and messenger RNA cytokine expression were evaluated before and after 6 months of HAART. All nine patients presented symptomatic retroviral infection. Early HAART was associated with a sustained and comparable reduction of HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs) and RSC biopsies. HIV DNA decreased in PBMCs, but was only marginally reduced in RSC biopsies. Comparisons between reduction rates of HIV DNA in these two compartments confirmed that HIV DNA clearance was less efficient in RSC biopsies compared with PBMCs. Assessment of immunological profiles in PBMCs and RSC biopsies showed that the T-helper (Th)1-like/Th2-like ratio was sharply decreased in RSC biopsies and increased in PBMCs throughout the study period. A persistent Th2-like profile was detected in RSC biopsies. Efficient clearing of HIV DNA observed in PBMCs correlated with the establishment of a more favourable Th1-like profile. A less efficient clearance of intracellular HIV DNA following early introduction of HAART is associated with persistent immunological impairment in gut-associated lymphoid tissue (GALT), which is reflected by the skewed expression of cytokines in this reservoir. The present study shows that early initiation of HAART, in the short-term, is not effective in containing the establishment of HIV infection and in reversing associated immunological GALT abnormalities.

  14. Morphologic observation of mucosa-associated lymphoid tissue in the large intestine of Bactrian camels (Camelus bactrianus).

    Science.gov (United States)

    ZhaXi, Yingpai; Wang, Wenhui; Zhang, Wangdong; Gao, Qiang; Guo, Minggang; Jia, Shuai

    2014-07-01

    The structure and distribution of the mucosa-associated lymphoid tissue (MALT) throughout the large intestine of 10 Bactrian camels were comparatively studied by anatomical and histological methods. The results showed that Peyer's patches (PPs) were mainly located on the mucosal surfaces of the entire ileocecal orifice, the beginning of the cecum and the first third of the colon. The shape of PPs gradually changed from "scrotiform" to "faviform" along the large intestine with the scrotiform PP as the major type in the ileocecal orifice. The distribution density also gradually decreased from the ileocecal orifice to the colon. The histological observations further revealed that the MALT in the form of PPs or isolated lymphoid follicles (ILF) and lamina propria lymphocytes was mainly present in the lamina propria and submucosa from the entire ileocecal orifice, where the muscularis mucosa is usually incomplete, to the colonic forepart. In addition, lymphoid tissue was much more abundant in the lamina propria and submucosa of the ileocecal orifice as compared to the cecum and colon. Statistically, the MALT of the ileocecal orifice contained a higher number of lymphoid follicles (37.7/10 mm(2) ) than that of the cecum, colon, or rectum (P lymphoid follicles were clearly visible. Together, our data suggest that the ileocecal orifice constitutes the main inductive site for the mucosal immunity in the large intestine of the Bactrian camel; and that scrotiform PPs are likely to the result of long-term adaptation of the Bactrian camel to the harsh living environment. © 2014 Wiley Periodicals, Inc.

  15. Artificial engineering of secondary lymphoid organs.

    Science.gov (United States)

    Tan, Jonathan K H; Watanabe, Takeshi

    2010-01-01

    Secondary lymphoid organs such as spleen and lymph nodes are highly organized immune structures essential for the initiation of immune responses. They display distinct B cell and T cell compartments associated with specific stromal follicular dendritic cells and fibroblastic reticular cells, respectively. Interweaved through the parenchyma is a conduit system that distributes small antigens and chemokines directly to B and T cell zones. While most structural aspects between lymph nodes and spleen are common, the entry of lymphocytes, antigen-presenting cells, and antigen into lymphoid tissues is regulated differently, reflecting the specialized functions of each organ in filtering either lymph or blood. The overall organization of lymphoid tissue is vital for effective antigen screening and recognition, and is a feature which artificially constructed lymphoid organoids endeavor to replicate. Synthesis of artificial lymphoid tissues is an emerging field that aims to provide therapeutic application for the treatment of severe infection, cancer, and age-related involution of secondary lymphoid tissues. The development of murine artificial lymphoid tissues has benefited greatly from an understanding of organogenesis of lymphoid organs, which has delineated cellular and molecular elements essential for the recruitment and organization of lymphocytes into lymphoid structures. Here, the field of artificial lymphoid tissue engineering is considered including elements of lymphoid structure and development relevant to organoid synthesis. (c) 2010 Elsevier Inc. All rights reserved.

  16. Derangements of lacrimal drainage-associated lymphoid tissue (LDALT) in human chronic dacryocystitis.

    Science.gov (United States)

    Ali, Mohammad Javed; Mulay, Kaustubh; Pujari, Aditi; Naik, Milind N

    2013-12-01

    To study the changes in the lacrimal drainage-associated lymphoid tissue of the lacrimal sac in human chronic dacryocystitis and its possible implications in understanding the immune defense mechanisms and etiopathogenesis of primary acquired nasolacrimal duct obstruction. Retrospective interventional study involving 200 lacrimal sacs of 164 consecutive patients seen between July 2009 and July 2012. Data collected include demographics, clinical presentation, laterality, age at presentation, duration of symptoms, diagnostic irrigation, indications for a dacyrocystectomy, pattern and severity of lymphoid infiltrate, types of lymphoid follicles and their locations, plasma cells, and other cellular infiltrates. The associated epithelial, stromal, and luminal changes with an emphasis on acini, mucosal glands, blood vessels, lymphatics, and goblet cells were also noted. Immunohistochemistry using CD3, CD20, CD138, and immunoglobulin A were used to substantiate the lymphoid tissues of the lacrimal sac. A total of 200 lacrimal sacs were obtained from dacryocystectomy of 164 patients. The patients included 60.5% (99/164) females and 39.6% (65/164) males, with a mean age of 58.4 years at presentation. Laterality showed a predominance of left lacrimal sacs (55%, 110/200) as compared to the right lacrimal sacs (45%, 90/200). Symptoms of epiphora and discharge of more than 6 months duration were considered to be chronic. Lymphoid infiltrate pattern was diffuse in majority of the sacs (81%, 162/200), with subepithelial and intraepithelial together being the commonest location (46.5%, 93/200). Distinct lymphoid follicles were seen in 28% (56/200). Most of the sacs showed mild plasma cell infiltration (66.5%, 133/200). IgA-rich secretions were noted in the lumen and the lining epithelium in 34.5% (69/200). Other common changes noted include increase in the goblet cells (82%, 164/200), dilated lymphatics (94%, 188/200), proliferating blood vessels (99%, 198/200), thickened

  17. 3'-Azido-2',3'-dideoxythymidine induced deficiency of thymidine kinases 1, 2 and deoxycytidine kinase in H9 T-lymphoid cells.

    Science.gov (United States)

    Gröschel, Bettina; Kaufmann, Andreas; Höver, Gerold; Cinatl, Jaroslav; Doerr, Hans Wilhelm; Noordhuis, Paul; Loves, Willem J P; Peters, Godefridus J; Cinatl, Jindrich

    2002-07-15

    Continuous cultivation of T-lymphoid H9 cells in the presence of 3'-azido-2',3'-dideoxythymidine (AZT) resulted in a cell variant cross-resistant to both thymidine and deoxycytidine analogs. Cytotoxic effects of AZT, 2',3'-didehydro-3'-deoxythymidine as well as different deoxycytidine analogs such as 2',3'-dideoxycytidine, 2',2'-difluoro-2'-deoxycytidine (dFdC) and 1-ss-D-arabinofuranosylcytosine (Ara-C) were strongly reduced in H9 cells continuously exposed to AZT when compared to parental cells (>8.3-, >6.6-, >9.1-, 5 x 10(4)-, 5 x 10(3)-fold, respectively). Moreover, anti-HIV-1 effects of AZT, d4T, ddC and 2',3'-dideoxy-3'-thiacytidine (3TC) were significantly diminished (>222-, >25-, >400-, >200-fold, respectively) in AZT-resistant H9 cells. Study of cellular mechanisms responsible for cross-resistance to pyrimidine analogs in AZT-resistant H9 cells revealed decreased mRNA levels of thymidine kinase 1 (TK1) and lack of deoxycytidine kinase (dCK) mRNA expression. The loss of dCK gene expression was confirmed by western blot analysis of dCK protein as well as dCK enzyme activity assay. Moreover, enzyme activity of TK1 and TK2 was reduced in AZT-resistant cells. In order to determine whether lack of dCK affected the formation of the active triphosphate of the deoxycytidine analog dFdC, dFdCTP accumulation and retention was measured in H9 parental and AZT-resistant cells after exposure to 1 and 10 microM dFdC. Parental H9 cells accumulated about 30 and 100 pmol dFdCTP/10(6) cells after 4hr, whereas in AZT-resistant cells no dFdCTP accumulation was detected. These results demonstrate that continuous treatment of H9 cells in the presence of AZT selected for a thymidine analog resistant cell variant with cross-resistance to deoxycytidine analogs, due to deficiency in TK1, TK2, and dCK.

  18. Impaired insulin signaling pathway in ovarian follicles of cows with cystic ovarian disease.

    Science.gov (United States)

    Hein, G J; Panzani, C G; Rodríguez, F M; Salvetti, N R; Díaz, P U; Gareis, N C; Benítez, G A; Ortega, H H; Rey, F

    2015-05-01

    Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. Follicular cell steroidogenesis and proliferation in ovulatory follicles is stimulated by hormones such as insulin and its necessary post-receptor response. The aim of this study was to determine the expression of insulin receptor (IR), IR substrate-1 (IRS1) and phosphatidylinositol 3-kinase (PI3K), key intermediates in the insulin pathway, in control cows and cows with spontaneous COD and ACTH-induced COD. IR and IRS1 mRNA levels were greater in granulosa cells and lower in follicular cysts than in control tertiary follicles. PI3K mRNA levels were similar in all follicles evaluated, whereas the expression of IR, IRS1 and PI3K was similar in theca cells. Protein expression of IR was higher in control tertiary follicles than in the same structures in animals with COD and with cysts. IRS1 and PI3K protein expression showed the same pattern in tertiary and cystic follicles. However, the protein expression of subunit alpha p85 of PI3K was greater in theca cells from tertiary follicles than in cystic follicles. These results provide new insights into the insulin response in cows with COD. The lower gene and protein expressions of some insulin downstream effectors at an early stage of the signaling pathway could negatively influence the functionality of ovaries and contribute to follicle persistence. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Generation of Immunoglobulin diversity in human gut-associated lymphoid tissue.

    Science.gov (United States)

    Spencer, Jo; Barone, Francesca; Dunn-Walters, Deborah

    2009-06-01

    The organised gut associated lymphoid tissue (GALT) exists adjacent to an extensive and diverse luminal flora. The follicle associated epithelium and associated dendritic cells and lymphocytes form a tightly fortified gateway between the flora and the host that permits connectivity between them and chronic activation of the lymphoid compartment. As a consequence, plasma cell precursors are generated continuously, and in abundance, in GALT by clonal proliferation. Clonal proliferation alone on this scale would reduce the spectrum of B cell specificity. To compensate, GALT also houses molecular machinery that diversifies the receptor repertoire by somatic hypermutation, class switch recombination and receptor revision. These three processes of enhancing the diversity of mature B cells ensure that although clonally related plasma cells may secrete immunoglobulin side by side in the mucosa they rarely have identical antigen binding sites.

  20. Innate lymphoid cells and asthma.

    Science.gov (United States)

    Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

    2014-04-01

    Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  1. Ante-mortem detection of chronic wasting disease in recto-anal mucosa-associated lymphoid tissues from elk (Cervus elaphus nelsoni) using real-time quaking-induced conversion (RT-QuIC) assay: A blinded collaborative study.

    Science.gov (United States)

    Manne, Sireesha; Kondru, Naveen; Nichols, Tracy; Lehmkuhl, Aaron; Thomsen, Bruce; Main, Rodger; Halbur, Patrick; Dutta, Somak; Kanthasamy, Anumantha G

    2017-11-02

    Prion diseases are transmissible spongiform encephalopathies (TSEs) characterized by fatal, progressive neurologic diseases with prolonged incubation periods and an accumulation of infectious misfolded prion proteins. Antemortem diagnosis is often difficult due to a long asymptomatic incubation period, differences in the pathogenesis of different prions, and the presence of very low levels of infectious prion in easily accessible samples. Chronic wasting disease (CWD) is a TSE affecting both wild and captive populations of cervids, including mule deer, white-tailed deer, elk, moose, muntjac, and most recently, wild reindeer. This study represents a well-controlled evaluation of a newly developed real-time quaking-induced conversion (RT-QuIC) assay as a potential CWD diagnostic screening test using rectal biopsy sections from a depopulated elk herd. We evaluated 69 blinded samples of recto-anal mucosa-associated lymphoid tissue (RAMALT) obtained from USDA Veterinary Services. The results were later un-blinded and statistically compared to immunohistochemical (IHC) results from the USDA National Veterinary Services Laboratories (NVSL) for RAMALT, obex, and medial retropharyngeal lymph node (MRPLN). Comparison of RAMALT RT-QuIC assay results with the IHC results of RAMALT revealed 92% relative sensitivity (95% confidence limits: 61.52-99.8%) and 95% relative specificity (95% confidence limits: 85.13-99%). Collectively, our results show a potential utility of the RT-QuIC assay to advance the development of a rapid, sensitive, and specific prion diagnostic assay for CWD prions.

  2. Type 2 innate lymphoid cells-new members of the "type 2 franchise" that mediate allergic airway inflammation

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2012-01-01

    Type 2 innate lymphoid cells (ILC2s) are members of an ILCfamily, which contains NKcells and Ror?t+ ILCs, the latter including lymphoid tissue inducer (LTi) cells and ILCs producing IL-17 and IL-22. ILC2s are dedicated to the production of IL-5 and IL-13 and, as such, ILC2s provide an early and

  3. Regulation of Cytokine Secretion in Human CD127(+) LTi-like Innate Lymphoid Cells by Toll-like Receptor 2

    NARCIS (Netherlands)

    Crellin, Natasha K.; Trifari, Sara; Kaplan, Charles D.; Satoh-Takayama, Naoko; Di Santo, James P.; Spits, Hergen

    2010-01-01

    Lymphoid tissue inducer cells are members of an emerging family of innate lymphoid cells (ILC). Although these cells were originally reported to produce cytokines such as interleukin-17 (IL-17) and IL-22, we demonstrate here that human CD127(+)RORC(+) and CD56(+)CD127(+) LTi-like ILC also express

  4. ID’ing Innate and Innate-like Lymphoid Cells

    Science.gov (United States)

    Verykokakis, Mihalis; Zook, Erin C.; Kee, Barbara L.

    2014-01-01

    Summary The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID:25123285

  5. ID'ing innate and innate-like lymphoid cells.

    Science.gov (United States)

    Verykokakis, Mihalis; Zook, Erin C; Kee, Barbara L

    2014-09-01

    The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B- and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Depletion and repopulation of lymphocytes in Peyer's patches of mice after total lymphoid irradiation

    International Nuclear Information System (INIS)

    Ermak, T.H.; Steger, H.J.; Owen, R.L.; Strober, S.

    1988-01-01

    The depletion and repopulation of lymphocytes in specific cellular domains of mouse Peyer's patches were examined following total lymphoid irradiation (TLI). BALB/c mice 5-months-old were given 17 fractionated doses of irradiation to a total of 3400 to 4250 rads over a 4-week period, and Peyer's patches were examined by immunohistochemistry at 1 to 4 days and 1 to 4 weeks after TLI. Cryostat sections were labeled with monoclonal antibodies directed against B220 (B cells), Thy-1.2 (all T cells), L3T4 (helper T cells), and Ly-2 (cytotoxic/suppressor T cells). In depleted mice, Peyer's patches were greatly reduced in size in comparison to controls, although the structural framework of follicles, domes, and interfollicular areas was still present. B cells in follicles were reduced to a small core of B220+ cells interspersed with nonlymphocytic cells. T cells were virtually eliminated from the patch except for a small population of Thy-1.2+ cells that were neither L3T4+ nor Ly-2+ in follicle domes. During early stages of repopulation at 1 to 2 weeks after TLI, follicles increased in size and were populated by helper T cells but Peyer's patches lacked discrete interfollicular T cell regions. At 3 to 4 weeks after TLI, T cell regions were found in interfollicular areas. The results indicate that morphologically distinct cellular domains are maintained in Peyer's patches after TLI which are sequentially repopulated by immigrating lymphocytes

  7. Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice.

    Science.gov (United States)

    Seys, Leen J M; Verhamme, Fien M; Dupont, Lisa L; Desauter, Elke; Duerr, Julia; Seyhan Agircan, Ayca; Conickx, Griet; Joos, Guy F; Brusselle, Guy G; Mall, Marcus A; Bracke, Ken R

    2015-01-01

    Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na⁺ channel (βENaC). βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.

  8. Hydrostatic pressure affects in vitro maturation of oocytes and follicles and increases granulosa cell death.

    Science.gov (United States)

    Rashidi, Zahra; Azadbakht, Mehri; Amini, Ali; Karimi, Isac

    2014-01-01

    This study examines the effects of hydrostatic pressure on in vitro maturation (IVM) of oocytes derived from in vitro grown follicles. In this experimental study, preantral follicles were isolated from 12-day-old female NMRI mice. Each follicle was cultured individually in Alpha Minimal Essential Medium (α-MEM) under mineral oil for 12 days. Then, follicles were induced for IVM and divided into two groups, control and experiment. In the experiment group follicles were subjected to 20 mmHg pressure for 30 minutes and cultured for 24-48 hours. We assessed for viability and IVM of the oocytes. The percentage of apoptosis in cumulus cells was determined by the TUNEL assay. A comparison between groups was made using the student's t test. The percentage of metaphase II oocytes (MII) increased in hydrostatic pressuretreated follicles compared to controls (phydrostatic pressure-treated follicles compared to controls (pHydrostatic pressure, by inducing apoptosis in cumulus cells, participates in the cumulus oocyte coupled relationship with oocyte maturation.

  9. [Eye-associated lymphoid tissue (EALT) is continuously spread throughout the ocular surface from the lacrimal gland to the lacrimal drainage system].

    Science.gov (United States)

    Knop, E; Knop, N

    2003-11-01

    Components of the mucosal immune system (MALT) have been identified in the conjunctiva (as CALT) and the lacrimal drainage system (as LDALT). Their structural and functional relation with the established immune protection by the lacrimal gland is unclear. Macroscopically normal and complete tissues of the conjunctiva, lacrimal drainage system and lacrimal gland from human body donors were investigated by analysis of translucent whole mounts, and using histology, immunohistology as well as scanning and transmission electron microscopy. A typical diffuse lymphoid tissue, composed of effector cells of the immune system (T-lymphocytes and IgA producing plasma cells) under an epithelium that contains the IgA transporter SC, is not isolated in the conjunctiva and lacrimal drainage system. It is anatomically continuous from the lacrimal gland along its excretory ducts into the conjunctiva and from there via the lacrimal canaliculi into the lacrimal drainage system. Lymphoid follicles occur in a majority (about 60%) and with bilateral symmetry. The topography of CALT corresponds to the position of the cornea in the closed eye. These results show that the MALT of the lacrimal gland, conjunctiva and lacrimal drainage system constitute an anatomical and functional unit for immune protection of the ocular surface. Therefore it should be integrated as an "eye-associated lymphoid tissue" (EALT) into the MALT system of the body. EALT can detect ocular surface antigens by the lymphoid follicles and can supply other organs and the ocular surface including the lacrimal gland with specific effector cells via the regulated recirculation of lymphoid cells.

  10. The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

    Science.gov (United States)

    Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

    2017-05-16

    Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

    Science.gov (United States)

    Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

    2008-04-01

    The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

  12. RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT).

    Science.gov (United States)

    Mutoh, Mami; Kimura, Shunsuke; Takahashi-Iwanaga, Hiromi; Hisamoto, Meri; Iwanaga, Toshihiko; Iida, Junichiro

    2016-04-01

    Murine nasopharynx-associated lymphoid tissue (NALT), located at the base of the nasal cavity, serves as a major site for the induction of mucosal immune responses against airway antigens. The follicle-associated epithelium (FAE) covering the luminal surface of NALT is characterized by the presence of microfold cells (M cells), which take up and transport luminal antigens to lymphocytes. Glycoprotein 2 (GP2) has recently been identified as a reliable marker for M cells in Peyer's patches of the intestine. However, the expression of GP2 and other functional molecules in the M cells of NALT has not yet been examined. We have immunohistochemically detected GP2-expressing cells in the FAE of NALT and the simultaneous expression of other intestinal M-cell markers, namely Tnfaip2, CCL9, and Spi-B. These cells have been further identified as M cells because of their higher uptake capacity of luminal microbeads. Electron microscopic observations have shown that GP2-expressing cells on the FAE display morphological features typical of M cells: they possess short microvilli and microfolds on the luminal surface and are closely associated with intraepithelial lymphocytes. We have also found that the receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed by stromal cells underneath the FAE, which provides its receptor RANK. The administration of RANKL markedly increases the number of GP2(+)Tnfaip2(+) cells on the NALT FAE and that of intestinal M cells. These results suggest that GP2(+)Tnfaip2(+) cells in NALT are equivalent to intestinal M cells, and that RANKL-RANK signaling induces their differentiation.

  13. Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    L Karimzadeh

    2012-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is a low grade inflammatory disease characterized by hyperandrogenemia and chronic anovulation. C-reactive protein (CRP, released by adipocytes, plays a key role in PCOS. Apis mellifera honeybee venom (HBV contains a variety of biologically active components with various pharmaceutical properties. This study was designed to assess the possibility of HBV application as an anti-inflammatory therapeutic agent. To induce PCOS, 1 mg/100 g body weight estradiol valerate (EV was subcutaneously (SC injected into eight-week-old rats. After 60 days, 0.5 mg/kg HBV was administered SC for 14 consecutive days, and the results of PCOS treatment were investigated. Rats were then anesthetized with chloroform, and their ovaries and livers were surgically removed to determine histomorphometrical changes. Testosterone and 17-β-estradiol were detected by chemiluminescence immunoassay. In order to detect serum CRP, ELISA kit was used in three groups of EV-induced PCOS, HBV-treated PCOS and control animals. Thickness of the theca layer, number of cysts and the level of serum CRP significantly decreased in HBV group in comparison with PCOS group. Moreover, corpus luteum, as a sign of ovulation, was observed in HBV-treated ovaries which were absent in PCOS group. Our results suggest that the beneficial effect of HBV may be mediated through its inhibitory effect on serum CRP levels.

  14. Effect of ovulatory follicle size and estradiol supplementation during the preovulatory period on pregnancy rates in postpartum beef cows

    Science.gov (United States)

    In postpartum beef cows, GnRH-induced ovulation of small dominant follicles decreased pregnancy rates and increased late embryonic/fetal mortality; however, ovulatory follicle size had no apparent effect on the establishment or maintenance of pregnancy when ovulation occurred spontaneously. Further...

  15. Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

    International Nuclear Information System (INIS)

    McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.

    1982-01-01

    Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease

  16. Shaping Innate Lymphoid Cell Diversity

    Directory of Open Access Journals (Sweden)

    Qiutong Huang

    2017-11-01

    Full Text Available Innate lymphoid cells (ILCs are a key cell type that are enriched at mucosal surfaces and within tissues. Our understanding of these cells is growing rapidly. Paradoxically, these cells play a role in maintaining tissue integrity but they also function as key drivers of allergy and inflammation. We present here the most recent understanding of how genomics has provided significant insight into how ILCs are generated and the enormous heterogeneity present within the canonical subsets. This has allowed the generation of a detailed blueprint for ILCs to become highly sensitive and adaptive sensors of environmental changes and therefore exquisitely equipped to protect immune surfaces.

  17. The pluripotency of hair follicle stem cells.

    Science.gov (United States)

    Hoffman, Robert M

    2006-02-01

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, is also expressed in follicle stem cells as well as their immediate differentiated progeny. The nestin-expressing hair follicle stem cells differentiated into neurons, glial cells, keratinocytes and smooth muscle cells in vitro. Hair-follicle stem cells were implanted into the gap region of a severed sciatic nerve. The hair follicle stem cells greatly enhanced the rate of nerve regeneration and the restoration of nerve function. The follicle stem cells transdifferentiated largely into Schwann cells which are known to support neuron regrowth. Function of the rejoined sciatic nerve was measured by contraction of the gastrocnemius muscle upon electrical stimulation. After severing the tibial nerve and subsequent transplantation of hair-follicle stem cells, the transplanted mice recovered the ability to walk normally. These results suggest that hair-follicle stem cells provide an important accessible, autologous source of adult stem cells for regenerative medicine.

  18. Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion.

    Science.gov (United States)

    Haley, Nicholas J; Siepker, Chris; Hoon-Hanks, Laura L; Mitchell, Gordon; Walter, W David; Manca, Matteo; Monello, Ryan J; Powers, Jenny G; Wild, Margaret A; Hoover, Edward A; Caughey, Byron; Richt, Jürgen A

    2016-04-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni;n= 323), and nasal brush samples were collected from a subpopulation of these animals (n= 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both thePRNPgenotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. Innate lymphoid cells in inflammation and immunity

    NARCIS (Netherlands)

    McKenzie, Andrew N. J.; Spits, Hergen; Eberl, Gerard

    2014-01-01

    Innate lymphoid cells (ILCs) were first described as playing important roles in the development of lymphoid tissues and more recently in the initiation of inflammation at barrier surfaces in response to infection or tissue damage. It has now become apparent that ILCs play more complex roles

  20. Lymphoid cells in chicken intestinal epithelium

    DEFF Research Database (Denmark)

    Bjerregaard, P

    1975-01-01

    The intraepithelial lymphoid cells of chicken small intestine were studied by light microscopy using 1 mu Epon sections, and by electron microscopy. Three cell types were found: small lymphocytes, large lymphoid cells, and granular cells. These cells correspond to the theliolymphocytes and globule...

  1. Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system.

    Science.gov (United States)

    Knop, E; Knop, N

    2001-03-01

    Mucosa-associated lymphoid tissue (MALT) specifically protects mucosal surfaces. In a previous study of the human conjunctiva, evidence was also found for the presence of MALT in the lacrimal sac. The present study, therefore, aims to investigate its morphology and topographical distribution in the human lacrimal drainage system. Lacrimal drainage systems (n = 51) obtained from human cadavers were investigated by clearing flat wholemounts or by serial sections of tissue embedded in paraffin, OCT compound, or epoxy resin. These were further analyzed by histology, immunohistochemistry, and electron microscopy. All specimens showed the presence of lymphocytes and plasma cells as a diffuse lymphoid tissue in the lamina propria, together with intraepithelial lymphocytes and occasional high endothelial venules (HEV). It formed a narrow layer along the canaliculi that became thicker in the cavernous parts. The majority of lymphocytes were T cells, whereas B cells were interspersed individually or formed follicular centers. T cells were positive for CD8 and the human mucosa lymphocyte antigen (HML-1). Most plasma cells were positive for IgA and the overlying epithelium expressed its transporter molecule secretory component (SC). Basal mucous glands were present in the lacrimal canaliculi and in the other parts accompanied by alveolar and acinar glands, all producing IgA-rich secretions. Primary and secondary lymphoid follicles possessing HEV were present in about half of the specimens. The term lacrimal drainage-associated lymphoid tissue (LDALT) is proposed here to describe the lymphoid tissue that is regularly present and belongs to the common mucosal immune system and to the secretory immune system. It is suggested that it may form a functional unit together with the lacrimal gland and conjunctiva, connected by tear flow, lymphocyte recirculation, and probably the neural reflex arc, and play a major role in preserving ocular surface integrity.

  2. Phytol isolated from watermelon (Citrullus lanatus) sprouts induces cell death in human T-lymphoid cell line Jurkat cells via S-phase cell cycle arrest.

    Science.gov (United States)

    Itoh, Tomohiro; Ono, Akito; Kawaguchi, Kaori; Teraoka, Sayaka; Harada, Mayo; Sumi, Keitaro; Ando, Masashi; Tsukamasa, Yasuyuki; Ninomiya, Masayuki; Koketsu, Mamoru; Hashizume, Toshiharu

    2018-05-01

    The phytol isolated from watermelon (Citrullus lanatus) sprouts inhibited the growth of a human T-cell leukemia line Jurkat cell and suppressed tumor progression in a xenograft model of human lung adenocarcinoma epithelial cell line A549 in nude mice. To elucidate the mechanisms underlying the phytol-induced cell death in the present study, we examined the changes in cell morphology, DNA fragmentation, and intracellular reactive oxygen species (ROS) levels and performed flow cytometric analysis to evaluate cell cycle stage. There were no significant changes in apoptosis, autophagy, and necrosis marker in cells treated with the phytol. But, we found, for the first time, that phytol remarkably induced S-phase cell cycle arrest accompanied with intracellular ROS production. Western blot analyses showed that phytolinduced S-phase cell cycle arrest was mediated through the decreased expression of cyclins A and D and the downregulations of MAPK and PI3K/Akt. The tumor volume levels in mice treated with phytol were lower than those of non-treatment groups, and it showed very similar suppression compared with those of mice treated with cyclophosphamide. Based on the data of in vitro and in vivo studies and previous studies, we suggest phytol as a potential therapeutic compound for cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    Science.gov (United States)

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

  4. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei, E-mail: weiwang2@illinois.edu; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbasava2@illinois.edu; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-01-15

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ► DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ► NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ► DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral

  5. Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Bei; Dou, Yannong; Wang, Ting; Yu, Juntao; Wu, Xin; Lu, Qian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China); Chou, Guixin; Wang, Zhengtao [Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Kong, Lingyi [Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Dai, Yue, E-mail: yuedaicpu@hotmail.com [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China); Xia, Yufeng, E-mail: yfxiacpu@126.com [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009 (China)

    2015-01-01

    Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic–pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3{sup +} cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR. - Highlights: • Norisoboldine, administered orally, markedly attenuates the clinical signs of CIA. • Norisoboldine regulates the balance of Th17/Treg cells in the intestinal lymph node. • Norisoboldine induces the migration of Treg cells from the gut to joint.

  6. Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues

    International Nuclear Information System (INIS)

    Tong, Bei; Dou, Yannong; Wang, Ting; Yu, Juntao; Wu, Xin; Lu, Qian; Chou, Guixin; Wang, Zhengtao; Kong, Lingyi; Dai, Yue; Xia, Yufeng

    2015-01-01

    Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic–pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3 + cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR. - Highlights: • Norisoboldine, administered orally, markedly attenuates the clinical signs of CIA. • Norisoboldine regulates the balance of Th17/Treg cells in the intestinal lymph node. • Norisoboldine induces the migration of Treg cells from the gut to joint

  7. Scrapie-specific pathology of sheep lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases often result in accumulation of disease-associated PrP (PrP(d in the lymphoreticular system (LRS, specifically in association with follicular dendritic cells (FDCs and tingible body macrophages (TBMs of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrP(d was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrP(d within endosomes and lysosomes. In addition, TBMs showed PrP(d in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrP(d is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrP(d/cell membrane interactions occur in different cell types.

  8. Phytohemagglutinin-induced change in the distribution of acidic sugars in surface membrane of lymphoid cells and blocking of the radiation effect

    International Nuclear Information System (INIS)

    Sato, C.; Kojima, K.

    1976-01-01

    Cell electrophoretic mobilities (EPM) of cultured lymphoblastoid cells were measured after removal of acidic sugars to investigate whether the localization of these acidic sugars was altered by the action of phytohaemagglutinin (PHA). After treatment with neuraminidase or hyaluronidase, the EPM of control cells decreased 50.1 and 0.3 percent, while that of PHA-treated cells decreased 25.2 and 39.0 percent, respectively. These results suggest that hyaluronic acid appeared at the periphery of the cell surface in place of some sialic acid after incubation with PHA. The change became evident after 10 min incubation with PHA and reached its maximum after 20 min at 37 0 C, but no change was observed at 4 0 C. The EPM decreased with time after x-irradiation, and reached a minimum value after 4 h. The addition of PHA to culture before irradiation completely blocked the x-ray mediated reduction in EPM. PHA administration after irradiation stopped further EPM reduction. These results seem to suggest a rapid rearrangement of membrane molecules linking with the receptors and acidic sugars induced by PHA, and blocking of further conformation change by x-irradiation

  9. Daunomycin accumulation and induction of programmed cell death in rat hair follicles

    DEFF Research Database (Denmark)

    Shin, Masashi; Larsson, Lars-Inge; Hougaard, David M.

    2009-01-01

    The anthracycline antibiotic daunomycin (DM) is useful for the treatment of leukemia but has side-effects such as alopecia. Using immunocytochemistry, we show that, after a single i.v. injection, DM accumulates in the nuclei of matrix cells and in the outer root sheath of hair follicles. DM......-positive matrix cells are detectable up to 48 h after injection and exhibit a characteristic granular morphology, which is not observed in saline-injected controls. TUNEL-staining has revealed that DM injection induces programmed cell death (PCD) in rat hair follicles. Cells undergoing PCD are detectable as late...... (PCD type 2). Interestingly, little, if any, DM accumulation or apoptosis has been detected in the dermal hair papillae. This may have a bearing on potential regeneration of the hair follicles. Thus, DM accumulates in a characteristic pattern in hair follicles. This accumulation is associated...

  10. Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues.

    Science.gov (United States)

    Tong, Bei; Dou, Yannong; Wang, Ting; Yu, Juntao; Wu, Xin; Lu, Qian; Chou, Guixin; Wang, Zhengtao; Kong, Lingyi; Dai, Yue; Xia, Yufeng

    2015-01-01

    Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic-pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3(+) cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. [The mantle zone in lymphatic follicles and its stratification].

    Science.gov (United States)

    Bednár, B

    1993-04-01

    Ten inguinal lymph nodes and spleens from autopsies were chosen according to age decades in order to get an idea about usual appearance of follicular structures. The group was complemented by 4 palatine tonsils from routine biopsies. Phenotype was ascertained by using about 30 standard markers and results were compared with a basic histocytological picture. The appearance of lymphatic tissue was quite different according to location and age categories, nevertheless, there were common immunophenotypic and structural features of follicular mantle in younger persons. It mostly comprised four cellular layers, more conspicuous at the upper pole of the follicle. An innermost layer was small-celled blastic, MB 2 and IgD positive, the next B monocytoid layer had medium sized cells of a similar phenotype but more alc, phosphatase positive. An inconstant plasmacytoid layer and a clarocellular layer used to be incomplete. It was cytostructurally characteristic but immunohistologically non-standard (faint CD 19 et CD 20 positivity). T 4 lymphocytes and perhaps some other elements leaving germinal centres were admixed into the inner mantle layer. Various small lymphoid cells, especially T 8 lymphocytes and sometimes litoral cells, were admixed into mantle periphery. Mutual exchange of lymphatic cells between the germinal and mantle zones was very scant. The mantle zone is presumed therefore to be independent from the structural and functional point of view as well.

  12. PREOVULATORY FOLLICLE DEVELOPMENT IN HIGH YIELDING COWS

    Directory of Open Access Journals (Sweden)

    Radovan Tomášek

    2013-06-01

    Full Text Available The aim of the study was to examine the development of preovulatory follicles in pregnant and non-pregnant high yielding cows. The treatment by supergestran and oestrophan was used to synchronize the estrous cycle. Ovaries were monitored by transrectal ultrasonography. The linear increase of preovulatory follicles was observed in pregnant (P < 0,001 and non-pregnant (P < 0,001 cows during 8 days before ovulation. In conclusion, preovulatory follicles in pregnant and non-pregnant high yielding cows developed similarly.

  13. In vivo confocal microscopy of conjunctiva-associated lymphoid tissue in healthy humans.

    Science.gov (United States)

    Agnifili, Luca; Mastropasqua, Rodolfo; Fasanella, Vincenzo; Di Staso, Silvio; Mastropasqua, Alessandra; Brescia, Lorenza; Mastropasqua, Leonardo

    2014-07-29

    To investigate modifications with aging of the presence, distribution and morphologic features of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects using laser scanning in vivo confocal microscopy (IVCM). A total of 108 (age range, 17-75 years) subjects were enrolled. In vivo confocal microscopy of the tarsal and bulbar conjunctiva, and impression cytology (IC) with CD3 (intra-epithelial T-lymphocytes) and CD20 (intra-epithelial B-lymphocytes) antibody immunofluorescence staining were performed. The main outcomes were subepithelial lymphocyte density (LyD), follicular density (FD), and follicular area (FA). The secondary outcomes were follicular reflectivity (FR), and lymphocyte density (FLyD), and CD3 and CD20 positivity. Conjunctiva-associated lymphoid tissue was observed in all subjects (97% only superior and 3% in both superior and inferior tarsum). Lymphocyte density ranged from 7.8 to 165.8 cells/mm(2) (46.42 [18.37]; mean [SD]), FD from 0.5 to 19.4 follicles/mm(2) (5.3 [3.6]), and FA from 1110 to 96,280 mm(2) (26,440 [26,280]). All three parameters showed a highly significant inverse cubic relationship with age (P lymphoid structures. These modifications may account for the decrease of mucosal immune response and increase of ocular surface diseases in the elderly. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  14. Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together

    Science.gov (United States)

    Jones, Gareth W.; Hill, David G.; Jones, Simon A.

    2016-01-01

    Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules. In this respect, they mimic the activities of germinal centers and contribute to the local control of adaptive immune responses. Studies in various disease settings have described how these structures contribute to either beneficial or deleterious outcomes. While the development and architectural organization of TLOs within inflamed tissues requires homeostatic chemokines, lymphoid and inflammatory cytokines, and adhesion molecules, our understanding of the cells responsible for triggering these events is still evolving. Over the past 10–15 years, novel immune cell subsets have been discovered that have more recently been implicated in the control of TLO development and function. In this review, we will discuss the contribution of these cell types and consider the potential to develop new therapeutic strategies that target TLOs. PMID:27752256

  15. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    Science.gov (United States)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  16. The Role of TOX in the Development of Innate Lymphoid Cells.

    Science.gov (United States)

    Seehus, Corey R; Kaye, Jonathan

    2015-01-01

    TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  17. Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.

  18. The Role of TOX in the Development of Innate Lymphoid Cells

    Directory of Open Access Journals (Sweden)

    Corey R. Seehus

    2015-01-01

    Full Text Available TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4+ T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  19. Tumor induction and hair follicle damage for different electron penetrations in rat skin

    International Nuclear Information System (INIS)

    Burns, F.J.; Sinclair, I.P.; Albert, R.E.; Vanderlaan, M.

    1976-01-01

    The penetration and dose of an electron beam were varied in an attempt to locate the depth in growing-phase rat skin where irradiation was most effective in inducing tumors and morphological damage to the hair follicles. The hair was plucked to initiate the growing phase of the hair cycle, and 12 days later the dorsal skin was irradiated with electrons penetrating 0.5, 1.0, or 2.0 mm at doses from 500 to 4000 rad. Differences in the curves of tumor incidence as a function of dose for different penetrations were best resolved by plotting the results against the 0.4 mm dose, while comparable curves for destruction of the follicles were best resolved by the 0.8 mm dose. Since 0.8 mm corresponded approximately to the depth of the follicles, these results indicated that the target tissues for follicular damage and tumor induction were separated in depth and that the target for tumor induction was probably located in the region above or near the midpoint of the follicles. When the radiation penetrated sufficiently to reach the entire follicle, the number of tumors produced was not significantly greater than the number observed previously in resting-phase skin, and it was inferred that the additional size and greater mitotic activity of the growing-phase follicles at the time of irradiation did not increase the probability of tumor induction

  20. Claudin expression in follicle-associated epithelium of rat Peyer's patches defines a major restriction of the paracellular pathway.

    Science.gov (United States)

    Markov, A G; Falchuk, E L; Kruglova, N M; Radloff, J; Amasheh, S

    2016-01-01

    Members of the tight junction protein family of claudins have been demonstrated to specifically determine paracellular permeability of the intestinal epithelium. In small intestinal mucosa, which is generally considered to be a leaky epithelium, Peyer's patches are a primary part of the immune system. The aim of this study was to analyse the tight junctional barrier of follicle-associated epithelium covering Peyer's patches (lymphoid follicles). Employing small intestinal tissue specimens of male Wistar rats, electrophysiological analyses including the Ussing chamber technique, marker flux measurements and one-path impedance spectroscopy were performed. Morphometry of HE-stained tissue sections was taken into account. Claudin expression and localization was analysed by immunoblotting and confocal laser scanning immunofluorescence microscopy. Almost twofold higher parameters of epithelial and transepithelial tissue resistance and a markedly lower permeability for the paracellular permeability markers 4 and 20 kDa FITC-dextran were detected in follicle-associated epithelium compared to neighbouring villous epithelium. Analysis of claudin expression and localization revealed a stronger expression of major sealing proteins in follicle-associated epithelium, including claudin-1, claudin-4, claudin-5 and claudin-8. Therefore, the specific expression and localization of claudins is in accordance with barrier properties of follicle-associated epithelium vs. neighbouring villous epithelium. We demonstrate that follicle-associated epithelium is specialized to ensure maximum restriction of the epithelial paracellular pathway in Peyer's patches by selective sealing of tight junctions. This results in an exclusive transcellular pathway of epithelial cells as the limiting and mandatory route for a controlled presentation of antigens to the underlying lymphocytes under physiological conditions. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. Common variable immunodeficiency in horses is characterized by B cell depletion in primary and secondary lymphoid tissues.

    Science.gov (United States)

    Flaminio, M Julia B F; Tallmadge, Rebecca L; Salles-Gomes, Cristina O M; Matychak, Mary Beth

    2009-01-01

    Common variable immunodeficiency (CVID) in horse patients is characterized by late-onset B cell lymphopenia or depletion, hypo- or agammaglobulinemia, impaired humoral response to tetanus toxoid vaccination, and recurrent fevers and bacterial infections. This study describes the clinical and immunologic findings of 14 affected horses (average age 10.7 +/- 4.4 years) of both genders (six females, eight males) and different breeds (eight Thoroughbreds, four Quarter Horses, one Warmblood, one Pony). Serial immunological testing in peripheral blood revealed persistent, severe B cell lymphopenia (mean 1.3 +/- 2.3% positive cells) in all patients. Serum IgG (range horses. Serum IgA concentrations declined with time. Histopathology and immunohistochemistry revealed absence of lymphoid follicles and B cells in primary and secondary lymphoid tissues. CVID is a cause of recurrent pneumonia, septicemia, and meningitis in adult horses and has a grave prognosis for clinical management and survival.

  2. Immunosuppressive effect of total lymphoid irradiation

    International Nuclear Information System (INIS)

    Bendel, V.; Medizinische Hochschule Hannover

    1981-01-01

    Contrary to the immunosuppression by means of wholebody irradiation which is known for a long while but connected with considerable side effects and risks, the total lymphoid irradiation (TLI) is a new possibility of immunosuppression the tolerance of which by man is known by virtue of long-standing experiences with the treatment of malignant lymphatic system diseases. In connexion with organ transplantations, TLI might possibly soon be important for the radiotherapeutist. In the experimentation on animals, the unspecific immunosuppression induced by TLI causes a prolonged survival time of allogeneic skin and organ grafts in certain mammals. Furthermore, a formation of blood chimeras combined with specific, permanent tolerance of organ grafts from the bone marrow donor can be caused by bone marrow transplantation after TLI. First experiences with man have been made. In the German literature, TLI has not been mentioned yet. In the present study, a summary is given on the Anglo-Saxon literature, and the first own experiments with regard to the problem of irradiation dose and transplantation interval are presented. (orig.) [de

  3. Innate lymphoid cells and their stromal microenvironments.

    Science.gov (United States)

    Kellermayer, Zoltán; Vojkovics, Dóra; Balogh, Péter

    2017-09-01

    In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  4. Molecular insights into the mechanisms of M-cell differentiation and transcytosis in the mucosa-associated lymphoid tissues.

    Science.gov (United States)

    Kimura, Shunsuke

    2018-01-01

    Microfold cells (M cells), which are located in the follicle-associated epithelium (FAE) covering mucosal lymphoid follicles, are specialized epithelial cells that initiate mucosal immune responses. These cells take luminal antigens and transport them via transcytosis across the FAE to the antigen-presenting cells underneath. Several intestinal pathogens exploit M cells as their portal for entry to invade the host and cause disease conditions. Recent studies have revealed that the uptake of antigens by M cells is essential for efficient antigen-specific IgA production and that this process likely maintains the homeostasis of mucosal tissues. The present article reviews recent advances in understanding the molecular mechanism of M-cell differentiation and describes the molecules expressed by M cells that are associated with antigen uptake and/or the transcytosis process. Current efforts to augment M-cell-mediated uptake for use in the development of effective mucosal vaccines are also discussed.

  5. Characteristics of nasal-associated lymphoid tissue (NALT) and nasal absorption capacity in chicken.

    Science.gov (United States)

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2013-01-01

    As the main mucosal immune inductive site of nasal cavity, nasal-associated lymphoid tissue (NALT) plays an important role in both antigen recognition and immune activation after intranasal immunization. However, the efficiency of intranasal vaccines is commonly restricted by the insufficient intake of antigen by the nasal mucosa, resulting from the nasal mucosal barrier and the nasal mucociliary clearance. The distribution of NALT and the characteristic of nasal cavity have already been described in humans and many laboratory rodents, while data about poultry are scarce. For this purpose, histological sections of the chicken nasal cavities were used to examine the anatomical structure and histological characteristics of nasal cavity. Besides, the absorptive capacity of chicken nasal mucosa was also studied using the materials with different particle size. Results showed that the NALT of chicken was located on the bottom of nasal septum and both sides of choanal cleft, which mainly consisted of second lymphoid follicle. A large number of lymphocytes were distributed under the mucosal epithelium of inferior nasal meatus. In addition, there were also diffuse lymphoid tissues located under the epithelium of the concha nasalis media and the walls of nasal cavity. The results of absorption experiment showed that the chicken nasal mucosa was capable to absorb trypan blue, OVA, and fluorescent latex particles. Inactivated avian influenza virus (IAIV) could be taken up by chicken nasal mucosa except for the stratified squamous epithelium sites located on the forepart of nasal cavity. The intake of IAIV by NALT was greater than that of the nasal mucosa covering on non-lymphoid tissue, which could be further enhanced after intranasal inoculation combined with sodium cholate or CpG DNA. The study on NALT and nasal absorptive capacity will be benefit for further understanding of immune mechanisms after nasal vaccination and development of nasal vaccines for poultry.

  6. Identification and characterization of novel gut-associated lymphoid tissues in rat small intestine.

    Science.gov (United States)

    Hitotsumatsu, Osamu; Hamada, Hiromasa; Naganuma, Makoto; Inoue, Nagamu; Ishii, Hiromasa; Hibi, Toshifumi; Ishikawa, Hiromichi

    2005-10-01

    The crypt lamina propria of the mouse small intestine has been shown to harbor multiple tiny clusters filled with c-kit- and interleukin 7 receptor (IL-7R)-positive lympho-hemopoietic cells (cryptopatches; CPs). However, it has remained an open question whether similar lymphoid tissue are present in the gastrointesitinal tract in other animals. In the present study, we investigated whether the small intestine of rats harbored lymphoid tissues similar to mouse CPs. Immunohistochemical and flow cytometric analyses were carried out using various antibodies, including those to c-kit and IL-7R molecules. Lymphocyte-filled villi (LFVs), populated predominantly with c-kit- and IL-7 receptor (IL-7R)-positive cells and less with T cell receptor (TCR)-alphabeta T cells were found throughout the small intestine of young adult rats. Although LFVs were absent from fetal rat intestine, they were first detected at around 2 weeks after birth. Notably, in most LFVs that settled in the antimesenteric wall of the small intestine in young adult rats, immunoglobulin M-positive B cells were also detectable at the bottom of the LFVs. In aged rats, lymphocytes in some LFVs displayed a different phenotype, comprising a large B-cell area that included a germinal center. Thus, these clusters represent the first description of isolated lymphoid follicles (ILFs) in the rat small intestine. The present study provides the first evidence for c-kit- and IL-7R-positive lymphocyte clusters in the rat small intestine. Our data also indicating that LFVs and ILFs may constitute novel organized gut-associated lymphoid tissues in lamina propria of the rat small intestine.

  7. HCV Virus and Lymphoid Neoplasms

    Directory of Open Access Journals (Sweden)

    Yutaka Tsutsumi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis.

  8. Scrambled and fried: Cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress

    International Nuclear Information System (INIS)

    Sobinoff, A.P.; Beckett, E.L.; Jarnicki, A.G.; Sutherland, J.M.; McCluskey, A.; Hansbro, P.M.; McLaughlin, E.A.

    2013-01-01

    Cigarette smoke is a reproductive hazard associated with pre-mature reproductive senescence and reduced clinical pregnancy rates in female smokers. Despite an increased awareness of the adverse effects of cigarette smoke exposure on systemic health, many women remain unaware of the adverse effects of cigarette smoke on female fertility. This issue is compounded by our limited understanding of the molecular mechanisms behind cigarette smoke induced infertility. In this study we used a direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease to characterise mechanisms of cigarette-smoke induced ovotoxicity. Cigarette smoke exposure caused increased levels of primordial follicle depletion, antral follicle oocyte apoptosis and oxidative stress in exposed ovaries, resulting in fewer follicles available for ovulation. Evidence of oxidative stress also persisted in ovulated oocytes which escaped destruction, with increased levels of mitochondrial ROS and lipid peroxidation resulting in reduced fertilisation potential. Microarray analysis of ovarian tissue correlated these insults with a complex mechanism of ovotoxicity involving genes associated with detoxification, inflammation, follicular activation, immune cell mediated apoptosis and membrane organisation. In particular, the phase I detoxifying enzyme cyp2e1 was found to be significantly up-regulated in developing oocytes; an enzyme known to cause molecular bioactivation resulting in oxidative stress. Our results provide a preliminary model of cigarette smoke induced sub-fertility through cyp2e1 bioactivation and oxidative stress, resulting in developing follicle depletion and oocyte dysfunction. - Highlights: • Cigarette smoke exposure targets developing follicle oocytes. • The antral follicle oocyte is a primary site of ovarian cigarette smoke metabolism. • Cyp2e1 is a major enzyme involved in ameliorating smoke-induced ovotoxicity. • Cigarette smoke causes oocyte

  9. Scrambled and fried: Cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Sobinoff, A.P. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); Beckett, E.L.; Jarnicki, A.G. [Centre for Asthma and Respiratory Disease, The University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308 (Australia); Sutherland, J.M. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); McCluskey, A. [Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia); Hansbro, P.M. [Centre for Asthma and Respiratory Disease, The University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308 (Australia); McLaughlin, E.A., E-mail: eileen.mclaughlin@newcastle.edu.au [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308 (Australia); Priority Research Centre for Chemical Biology, University of Newcastle, Callaghan, NSW 2308 (Australia)

    2013-09-01

    Cigarette smoke is a reproductive hazard associated with pre-mature reproductive senescence and reduced clinical pregnancy rates in female smokers. Despite an increased awareness of the adverse effects of cigarette smoke exposure on systemic health, many women remain unaware of the adverse effects of cigarette smoke on female fertility. This issue is compounded by our limited understanding of the molecular mechanisms behind cigarette smoke induced infertility. In this study we used a direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease to characterise mechanisms of cigarette-smoke induced ovotoxicity. Cigarette smoke exposure caused increased levels of primordial follicle depletion, antral follicle oocyte apoptosis and oxidative stress in exposed ovaries, resulting in fewer follicles available for ovulation. Evidence of oxidative stress also persisted in ovulated oocytes which escaped destruction, with increased levels of mitochondrial ROS and lipid peroxidation resulting in reduced fertilisation potential. Microarray analysis of ovarian tissue correlated these insults with a complex mechanism of ovotoxicity involving genes associated with detoxification, inflammation, follicular activation, immune cell mediated apoptosis and membrane organisation. In particular, the phase I detoxifying enzyme cyp2e1 was found to be significantly up-regulated in developing oocytes; an enzyme known to cause molecular bioactivation resulting in oxidative stress. Our results provide a preliminary model of cigarette smoke induced sub-fertility through cyp2e1 bioactivation and oxidative stress, resulting in developing follicle depletion and oocyte dysfunction. - Highlights: • Cigarette smoke exposure targets developing follicle oocytes. • The antral follicle oocyte is a primary site of ovarian cigarette smoke metabolism. • Cyp2e1 is a major enzyme involved in ameliorating smoke-induced ovotoxicity. • Cigarette smoke causes oocyte

  10. Dynamics of extracellular matrix in ovarian follicles and corpora lutea of mice

    DEFF Research Database (Denmark)

    Irving-Rodgers, Helen F; Hummitzsch, Katja; Murdiyarso, Lydia S

    2009-01-01

    Despite the mouse being an important laboratory species, little is known about changes in its extracellular matrix (ECM) during follicle and corpora lutea formation and regression. Follicle development was induced in mice (29 days of age/experimental day 0) by injections of pregnant mare's serum...... and antral follicles. The focimatrix, a specialised matrix of the membrana granulosa, contained collagen type IV alpha1 and alpha2, laminin alpha1, beta1 and gamma1 chains, nidogens 1 and 2, perlecan and collagen type XVIII. In the corpora lutea, staining was restricted to capillary sub-endothelial basal...... gonadotrophin on days 0 and 1 and ovulation was induced by injection of human chorionic gonadotrophin on day 2. Ovaries were collected for immunohistochemistry (n=10 per group) on days 0, 2 and 5. Another group was mated and ovaries were examined on day 11 (n=7). Collagen type IV alpha1 and alpha2, laminin...

  11. Unravelling hair follicle-adipocyte communication.

    Science.gov (United States)

    Schmidt, Barbara; Horsley, Valerie

    2012-11-01

    Here, we explore the established and potential roles for intradermal adipose tissue in communication with hair follicle biology. The hair follicle delves deep into the rich dermal macroenvironment as it grows to maturity where it is surrounded by large lipid-filled adipocytes. Intradermal adipocytes regenerate with faster kinetics than other adipose tissue depots and in parallel with the hair cycle, suggesting an interplay exists between hair follicle cells and adipocytes. While adipocytes have well-established roles in metabolism and energy storage, until recently, they were overlooked as niche cells that provide important growth signals to neighbouring skin cells. We discuss recent data supporting adipocytes as niche cells for the skin and skin pathologies that may be related to alterations in skin adipose tissue defects. © 2012 John Wiley & Sons A/S.

  12. Total lymphoid irradiation for multiple sclerosis

    International Nuclear Information System (INIS)

    Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

    1988-01-01

    Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one

  13. TOX sets the stage for innate lymphoid cells

    NARCIS (Netherlands)

    Spits, Hergen

    2015-01-01

    Like T cells and B cells, innate lymphoid cells (ILCs) develop from common lymphoid progenitors, but how commitment to the ILC lineage is regulated has remained unclear. The transcriptional regulator TOX is important in this process

  14. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    International Nuclear Information System (INIS)

    Trentham, D.E.; Belli, J.A.; Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-01-01

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered

  15. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    International Nuclear Information System (INIS)

    Trentham, D.E.; Belli, J.A.; Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-01-01

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly before a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered

  16. Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

    DEFF Research Database (Denmark)

    Schrama, D.; Voigt, H.; Eggert, A.O.

    2008-01-01

    BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...... response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction...... of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells...

  17. A rear case of multilocular thymic cyst with follicular lymphoid hyperplasia; Radiologic and histopathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Suk; Cha, Eun Jung [Konyang University Hospital, Daejeon (Korea, Republic of)

    2016-06-15

    Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose.

  18. The "vanishing follicle" in women with low number of developing follicles during assisted reproduction.

    Science.gov (United States)

    Younis, Johnny S; Yakovi, Shiran; Izhaki, Ido; Haddad, Sami; Ben-Ami, Moshe

    2018-01-01

    To investigate the occurrence of the "vanishing follicle" phenomenon in women with low number of developing follicles in assisted reproduction. Women with ≤ 6 follicles on the day of hCG administration with ≥ 14mm diameter were prospectively studied. Primary outcome measures were disappearance of ≥14mm and all-diameter follicles on the day of oocyte pick-up compared to the day of hCG administration. Among the 120 women recruited, 95 were found eligible and completed the study. The "vanishing follicle" phenomenon occurred in 3.1% (95% confidence level: 0.7%-9.0%) and 18.9% (95% confidence level: 11.6%-28.3%) of cases affecting ≥14mm and all-diameter follicles, respectively. In all cases, mid-late follicular serum LH and P levels remained within normal follicular phase range and trans-vaginal scan did not show signs of ovulation. Markedly, the main significant difference between the study and control groups in the ≥14mm follicle group was serum E 2 level on the day of hCG administration; median (Interquartile range), corresponding to 395 (382.0-405.5) versus 823.0 (544.5-1291.0) pg/mL, respectively (P=0.04). The same trend was encountered in all-diameter vanishing follicles group but it did not reach significance. Interestingly, in all-diameter vanishing group, chronic smoking and the P/E 2 ratio on the hCG day were significantly higher than controls. Post hoc multiple logistic regression analysis of data in accordance with the Bologna criteria reveled that antral follicle count was found to significantly affect the development of the "vanishing follicle" phenomenon. The "vanishing follicle" phenomenon occasionally occurs in women with low number of developing follicles during assisted reproduction with no signs of ovulation. Our preliminary findings suggest that this phenomenon may be related to exhausted ovarian reserve however, an early-unrecognized LH elevation could not be ruled out. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Immunosuppression and tolerance after total lymphoid irradiation (TLI)

    International Nuclear Information System (INIS)

    Strober, S.; Gottlieb, M.; Slavin, S.; King, D.P.; Hoppe, R.T.; Fuks, Z.; Bieber, C.P.; Kaplan, H.S.

    1980-01-01

    The immunosuppressive effects of total lymphoid irradiation (TLI) in humans and in several species of inbred and outbred laboratory animals have been investigated. A unique property of TLI, the prevention of the graft vs. host disease, was used to induce transplantation tolerance in order to study the mechanism of altered immunity when the celluar basis of the TLI-induced immunosuppression was examined by means of the mixed lymphocyte response (MLR), no suppression of the MLR was observed when spleen cells from unirradiated or whole body-irradiated donors were used instead of donors given TLI. These results indicated that TLI induces a population of cells in the spleen that can nonspecifically suppress the MLR

  20. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    OpenAIRE

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of ly...

  1. Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Plesner, T; Larsen, J K

    1985-01-01

    than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group of age matched......The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin....... A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced expression...

  2. In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.

    Science.gov (United States)

    Lew, Y Y; Michalak, T I

    2001-02-01

    Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.

  3. Mybs in mouse hair follicle development

    Czech Academy of Sciences Publication Activity Database

    Veselá, Barbora; Švandová, Eva; Šmarda, J.; Matalová, Eva

    2014-01-01

    Roč. 46, č. 5 (2014), s. 352-355 ISSN 0040-8166 R&D Projects: GA ČR GCP302/12/J059 Institutional support: RVO:67985904 Keywords : hair follicle * stem cells * c-Myb * B-Myb * development Subject RIV: EA - Cell Biology Impact factor: 1.252, year: 2014

  4. Development of venetoclax for therapy of lymphoid malignancies

    Directory of Open Access Journals (Sweden)

    Zhu H

    2017-03-01

    Full Text Available Huayuan Zhu,1,2 Alexandru Almasan1 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; 2Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China Abstract: B-cell lymphoma-2 (BCL-2 family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199 is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients. Also, unlike the other targeted agents, it is effective against tumor cells that reside in the blood marrow. Despite its promising outcome in CLL, preclinical data have already uncovered mechanistic insights underlying venetoclax resistance, such as upregulation of MCL-1 or BCL-xL expression and protective signaling from the microenvironment. In this review, we describe the role of the BCL-2 family in the pathogenesis of B-cell lymphoid malignancies, the development of venetoclax, and its current clinical outcome in CLL and other B-cell malignancies. We also discuss the resistance mechanisms that develop following venetoclax therapy, potential strategies to overcome them, and how this knowledge can be translated into clinical applications. Keywords: BCL-2, BCL-xL, chronic lymphocytic leukemia, MCL-1, venetoclax

  5. Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro

    International Nuclear Information System (INIS)

    Gupta, Rupesh K.; Singh, Jeffery M.; Leslie, Tracie C.; Meachum, Sharon; Flaws, Jodi A.; Yao, Humphrey H-C

    2010-01-01

    Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in a wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) decrease serum estradiol levels and aromatase (Arom) expression, prolong estrous cycles, and cause anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1-100 μg/ml) and MEHP (0.1-10 μg/ml) directly inhibit antral follicular growth and estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 h. During culture, follicle size was measured every 24 h as a measurement of follicle growth. After culture, media were collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at the highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom at the highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.

  6. The biology of human innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, J.H.J.

    2016-01-01

    In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology. First I

  7. Innate lymphoid cells, precursors and plasticity.

    Science.gov (United States)

    Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

    2016-11-01

    Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation. There, ILC contribute to the first line defense as well as to organ homeostasis. However, ILC are not only involved in classical defense tasks, but also contribute to the organogenesis of lymphoid organs as well as tissue remodeling and even stem cell regeneration. ILC may, therefore, implement different functions according to their emergence in ontogeny, their development and their final tissue location. We will review here their early development from precursors of the fetal liver and the adult bone marrow as well as their late plasticity in adaptation to their environment. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  8. Radiotherapy of lymphoid diseases of the orbit

    International Nuclear Information System (INIS)

    Austin-Seymour, M.M.; Donaldson, S.S.; Egbert, P.R.; McDougall, I.R.; Kriss, J.P.

    1985-01-01

    Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. Two patients developed cataracts. Carefullly planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma

  9. Homing of bone marrow lymphoid cells

    International Nuclear Information System (INIS)

    Yoshida, Y.; Osmond, D.G.

    1978-01-01

    DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

  10. The new WHO nomenclature: lymphoid neoplasms.

    Science.gov (United States)

    Leclair, Susan J; Rodak, Bernadette F

    2002-01-01

    The development of the WHO classification of lymphoid neoplasms is a remarkable example of cooperation and communication between pathologists and oncologists from around the world. Joint classification committees of the major hematopathology societies will periodically review and update this classification, facilitating further progress in the understanding and treatment of hematologic malignancies.

  11. Conjunctival lymphoma arising from reactive lymphoid hyperplasia

    Directory of Open Access Journals (Sweden)

    Fukuhara Junichi

    2012-09-01

    Full Text Available Abstract Extra nodal marginal zone B-cell lymphoma (EMZL of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU. Specimens from conjunctival tumors in the right eye, oculus dexter (OD, revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS, and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.

  12. Mapping of NKp46+ cells in healthy human lymphoid and non-lymphoid tissues

    Directory of Open Access Journals (Sweden)

    Elena eTomasello

    2012-11-01

    Full Text Available Understanding Natural Killer (NK cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs expressing the retinoic acid receptor-related orphan receptor t (RORt transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORt+ILCs with a lineage-CD94-CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.

  13. Mapping of NKp46+ Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues

    Science.gov (United States)

    Tomasello, Elena; Yessaad, Nadia; Gregoire, Emilie; Hudspeth, Kelly; Luci, Carmelo; Mavilio, Domenico; Hardwigsen, Jean; Vivier, Eric

    2012-01-01

    Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor γt (RORγt) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs, and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORγt+ ILCs with a lineage−CD94−CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases. PMID:23181063

  14. Distribution of lymphocyte subsets in the small intestine lymphoid tissue of 1-month-old lambs.

    Science.gov (United States)

    Corpa, J M; Juste, R A; García Marín, J F; Reyes, L E; González, J; Pérez, V

    2001-04-01

    Distribution of lymphocyte subpopulations along the small intestine lymphoid tissue has been examined in 1-month-old lambs using flow cytometric and immunohistochemical techniques. Monoclonal antibodies against CD4, CD8, gamma delta, CD45R and B receptors have been employed in samples from continuous ileal Peyer's patch (IPP), discrete jejunal Peyer's patches (JPP), ileocaecal valve lymphoid tissue (ICVPP), mesenteric lymph node (MLN) and intra-epithelial (IEL) and lamina propria (LPL) lymphocytes. Histological studies were also done. Differences in the lymphocyte distribution have been observed between some of the regions examined, especially between IPP and JPP for most of the markers. A remarkable feature was the existence of morphological and lymphocyte distribution differences between ICVPP and IPP, locations that had been traditionally considered as similar. The antibody against CD45R receptor used in this study, that was supposed to mark B cells and some T cells, detected cell populations located in the dome of the follicles in all the samples, whereas the centre was negative. Lymphocytes positive to the B marker employed were located mainly in the centre, suggesting that both antibodies would mark B cells in different maturation status.

  15. [Clinicopathologic features of primary hepatic marginal zone lymphoma of mucosa-associated lymphoid tissue and hepatic pseudolymphoma].

    Science.gov (United States)

    Liu, C; Li, X; Li, H; Gong, Q X; Li, Y; Wang, Z; Zhang, Z H

    2018-01-08

    Objective: To study the clinicopathological features of primary hepatic extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) and hepatic pseudolymphoma, and to discuss their differential diagnosis, treatment and prognosis. Methods: Three primary hepatic MALT lymphomas and two hepatic pseudolymphomas collected from January 2012 to March 2017 in the First Affiliated Hospital of Nanjing Medical University were evaluated by HE and immunohistochemistry(IHC), in-situ hybridization and immunoglobulin (Ig) gene rearrangement detection, and the relevant literature reviewed. Results: In the three MALT lymphomas, tumor cells infiltrated the portal areas with nodular pattern, and invaded the surrounding normal liver with serpiginous configuration and formation of confluent sheets. A number of bile ducts were entrapped within the lesions, and showed lymphoepithelial lesion. Reactive lymphoid follicles were present and surrounded by tumor cells, consisting of predominantly centrocyte-like cells and monocytoid B cells. There were clusters of epithelioid histiocytes in one case. The tumor cells were positive for CD20, PAX5 and negative for CD5, CD23, CD10, bcl-6, and cyclin D1. In the two hepatic pseudolymphomas, the lesions presented as solitary nodules well-demarcated from the surrounding liver tissue; one case was partially encapsulated with fibrous tissue. Entrapped bile ducts were only found at the edge of the lesions without lymphoepithelial lesion. The lesions comprised of massive lymphoid proliferation consisting predominantly of reactive lymphoid follicles, but not monocytoid B-cells or atypical cells. By IHC, a mixture of B- and T-cell population was identified. A monoclonal rearrangement of the Ig gene was detected in all three MALT lymphomas but not in two pseudolymphomas. Interphase fluorescence in situ hybridiazation test for MALT1 break-apart gene was positive in two cases of MALT lymphomas and EBER was negative in all studied cases

  16. Human innate lymphoid cells (ILCs) in filarial infections.

    Science.gov (United States)

    Bonne-Année, S; Nutman, T B

    2018-02-01

    Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  17. The Yin and Yang of Innate Lymphoid Cells in Cancer.

    Science.gov (United States)

    Carrega, Paolo; Campana, Stefania; Bonaccorsi, Irene; Ferlazzo, Guido

    2016-11-01

    The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  18. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy

  19. Nasal-associated lymphoid tissues (NALTs) support the recall but not priming of influenza virus-specific cytotoxic T cells.

    Science.gov (United States)

    Pizzolla, Angela; Wang, Zhongfang; Groom, Joanna R; Kedzierska, Katherine; Brooks, Andrew G; Reading, Patrick C; Wakim, Linda M

    2017-05-16

    The lymphoid tissue that drains the upper respiratory tract represents an important induction site for cytotoxic T lymphocyte (CTL) immunity to airborne pathogens and intranasal vaccines. Here, we investigated the role of the nasal-associated lymphoid tissues (NALTs), which are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage, in the initial priming and recall expansion of CD8 + T cells following an upper respiratory tract infection with a pathogenic influenza virus and immunization with a live attenuated influenza virus vaccine. Whereas NALTs served as the induction site for the recall expansion of memory CD8 + T cells following influenza virus infection or vaccination, they failed to support activation of naïve CD8 + T cells. Strikingly, NALTs, unlike other lymphoid tissues, were not routinely surveyed during the steady state by circulating T cells. The selective recruitment of memory T cells into these lymphoid structures occurred in response to infection-induced elevation of the chemokine CXCL10, which attracted CXCR3 + memory CD8 + T cells. These results have significant implications for intranasal vaccines, which deliver antigen to mucosal-associated lymphoid tissue and aim to elicit protective CTL-mediated immunity.

  20. Central Role of Core Binding Factor β2 in Mucosa-Associated Lymphoid Tissue Organogenesis in Mouse.

    Science.gov (United States)

    Nagatake, Takahiro; Fukuyama, Satoshi; Sato, Shintaro; Okura, Hideaki; Tachibana, Masashi; Taniuchi, Ichiro; Ito, Kosei; Shimojou, Michiko; Matsumoto, Naomi; Suzuki, Hidehiko; Kunisawa, Jun; Kiyono, Hiroshi

    2015-01-01

    Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer's patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) β2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3-CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbfβ2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbfβ2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbfβ2-/- mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbfβ2-/- mice. These findings demonstrate that Cbfβ2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT.

  1. Innate Lymphoid Cells in Intestinal Inflammation

    Science.gov (United States)

    Geremia, Alessandra; Arancibia-Cárcamo, Carolina V.

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an increased risk of

  2. Innate Lymphoid Cells in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Alessandra Geremia

    2017-10-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an

  3. Ion beam microanalysis of human hair follicles

    International Nuclear Information System (INIS)

    Kertesz, Zs.; Szikszai, Z.; Telek, A.; Biro, T.; Debrecen Univ.

    2006-01-01

    Complete text of publication follows. Hair follicle (HF) is an appendage organ of the skin which is of importance to the survival of mammals and still maintains significance for the human race - not just biologically, but also through cosmetic and commercial considerations. However data on the composition of hair follicles are scarce and mostly limited to the hair shaft. In addition, to the best of our knowledge, no data are available concerning the distribution of elements in human hair follicle with various growth and cycling phases. In this study [1] we provided detailed quantitative elemental distribution of organ-cultured hair follicle in anagen and catagen growth phases using ion microscopy in order to reach a better understanding of the function, development, and cyclic activity of the hair follicle. The microprobe analysis was carried out at the scanning ion microprobe facilities at the ATOMKI Debrecen, and at the Jozef Stefan Institute, Ljubljana, Slovenia, using combined STIM and PIXE ion beam analytical techniques. Human anagen hair follicles were isolated from skin obtained from females undergoing face-lift surgery. Cultured anagen HFs were treated by either vehicle or by 10 μM capsaicin for 5 days. Elemental distributions and absolute concentrations were determined along 5 capsaicin treated (catagen), and 4 control (anagen) hair follicles. The investigated length varied between 1.5 and 2 mm. Average elemental concentration values of the whole sample and the different morphological parts were also determined. Concentrations for most of the elements were found to be the same in the corresponding parts of the anagen and the catagen hair follicles. However, significant differences were observed in the Ca concentration between the anagen and catagen HFs. With respect to the distribution of Ca, in anagen (control) HFs, the following concentrations were measured (given in μg/g dry weight): dermal papilla, ∼500; matrix of the bulb, 1000-1500; outer/ inner

  4. CXCR5-Dependent Entry of CD8 T Cells into Rhesus Macaque B-Cell Follicles Achieved through T-Cell Engineering.

    Science.gov (United States)

    Ayala, Victor I; Deleage, Claire; Trivett, Matthew T; Jain, Sumiti; Coren, Lori V; Breed, Matthew W; Kramer, Joshua A; Thomas, James A; Estes, Jacob D; Lifson, Jeffrey D; Ott, David E

    2017-06-01

    Follicular helper CD4 T cells, T FH , residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXC chemokine receptor 5 (CXCR5), the chemokine receptor implicated in cellular entry into B-cell follicles. Engineered CD8 T cells expressing human CXCR5 (CD8 hCXCR5 ) exhibited ligand-specific signaling and chemotaxis in vitro Six infected rhesus macaques were infused with differentially fluorescent dye-labeled autologous CD8 hCXCR5 and untransduced CD8 T cells and necropsied 48 h later. Flow cytometry of both spleen and lymph node samples revealed higher frequencies of CD8 hCXCR5 than untransduced cells, consistent with preferential trafficking to B-cell follicle-containing tissues. Confocal fluorescence microscopy of thin-sectioned lymphoid tissues demonstrated strong preferential localization of CD8 hCXCR5 T cells within B-cell follicles with only rare cells in extrafollicular locations. CD8 hCXCR5 T cells were present throughout the follicles with some observed near infected T FH In contrast, untransduced CD8 T cells were found in the extrafollicular T-cell zone. Our ability to direct localization of unselected CD8 T cells into B-cell follicles using CXCR5 expression provides a strategy to place highly effective virus-specific CD8 T cells into these AIDS virus sanctuaries and potentially suppress residual viral replication. IMPORTANCE AIDS virus persistence in individuals under effective drug therapy or those who spontaneously control viremia remains an obstacle to definitive treatment. Infected follicular helper CD4 T cells, T FH , present inside B-cell follicles represent a

  5. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

    Energy Technology Data Exchange (ETDEWEB)

    Craig, Zelieann R., E-mail: zelieann@illinois.edu; Hannon, Patrick R., E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2013-11-01

    in mono-OH MXC-treated follicles. • Pregnenolone did not prevent mono-OH MXC-induced inhibition of growth and survival.

  6. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

    International Nuclear Information System (INIS)

    Craig, Zelieann R.; Hannon, Patrick R.; Flaws, Jodi A.

    2013-01-01

    -treated follicles. • Pregnenolone did not prevent mono-OH MXC-induced inhibition of growth and survival

  7. In-vivo effects of lipopolysaccharide on lymphoid and non-lymphoid cells in the mouse spleen. Migration of marginal metallophils towards the follicle centres

    NARCIS (Netherlands)

    Groeneveld, P. H.; van Rooijen, N.; Eikelenboom, P.

    1983-01-01

    In mice marginal metallophils are located at the periphery of the white pulp along the inner border of the marginal sinus. These cells have a weak phagocytic capacity but their function is still unclear. In the present study evidence is given that marginal metallophils migrate from the periphery of

  8. Tertiary lymphoid structures in cancer and beyond.

    Science.gov (United States)

    Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolas A; Sautès-Fridman, Catherine; Fridman, Wolf Herman

    2014-11-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. STUDIES ON TRANSMISSIBLE LYMPHOID LEUCEMIA OF MICE.

    Science.gov (United States)

    Furth, J; Strumia, M

    1931-04-30

    Lymphoid leucemia of the mouse is readily transmitted by intravenous inoculations. The majority of the mice inoculated successfully develop leucemic, a smaller number of them, aleucemic lymphadenosis. The data presented favor the view that leucemic and aleucemic lymphadenosis are essentially the same condition. Leucemia produced by transmission is preceded by an aleucemic stage, in which the lymph nodes and the spleen are uniformly enlarged, and the white blood count and the percentage of lymphocytes are within the normal range but immature lymphocytes are numerous in the circulating blood. Young as well as old mice may develop leucemia if leucotic material enters their circulation. Studies of transmissible leucemia favor the view that leucemia of mammals is a neoplastic disease. The basic problem of leucemia would seem to be determination of the factors that bring about a malignant transformation of lymphoid cells.

  10. Effect of antiprogesterone RU486 on VEGF expression and blood vessel remodeling on ovarian follicles before ovulation.

    Directory of Open Access Journals (Sweden)

    Annunziata Mauro

    Full Text Available BACKGROUND: The success of ovarian follicle growth and ovulation is strictly related to the development of an adequate blood vessel network required to sustain the proliferative and endocrine functions of the follicular cells. Even if the Vascular Endothelial Growth Factor (VEGF drives angiogenesis before ovulation, the local role exerted by Progesterone (P₄ remains to be clarified, in particular when its concentration rapidly increases before ovulation. AIM: This in vivo study was designed to clarify the effect promoted by a P₄ receptor antagonist, RU486, on VEGF expression and follicular angiogenesis before ovulation, in particular, during the transition from pre to periovulatory follicles induced by human Chorionic Gonadotropins (hCG administration. MATERIAL AND METHODS: Preovulatory follicle growth and ovulation were pharmacologically induced in prepubertal gilts by combining equine Chorionic Gonadotropins (eCG and hCG used in the presence or absence of RU486. The effects on VEGF expression were analyzed using biochemical and immunohistochemical studies, either on granulosa or on theca layers of follicles isolated few hours before ovulation. This angiogenic factor was also correlated to follicular morphology and to blood vessels architecture. RESULTS AND CONCLUSIONS: VEGF production, blood vessel network and follicle remodeling were impaired by RU486 treatment, even if the cause-effect correlation remains to be clarified. The P₄ antagonist strongly down-regulated theca VEGF expression, thus, preventing most of the angiogenic follicle response induced by hCG. RU486-treated follicles displayed a reduced vascular area, a lower rate of endothelial cell proliferation and a reduced recruitment of perivascular mural cells. These data provide important insights on the biological role of RU486 and, indirectly, on steroid hormones during periovulatory follicular phase. In addition, an in vivo model is proposed to evaluate how periovulatory

  11. Tertiary lymphoid organs in Takayasu Arteritis

    OpenAIRE

    Marc eClement; Marc eClement; Adrien eGaly; Patrick eBruneval; Marion eMorvan; Fabien eHyafil; Fabien eHyafil; Khadija eBenali; Nicoletta ePasi; Lydia eDeschamps; Quentin ePellenc; Quentin ePellenc; Thomas ePapo; Antonino eNicoletti; Antonino eNicoletti

    2016-01-01

    Objective: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients.Methods: Hematoxylin and eosin–stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from t...

  12. Tertiary Lymphoid Organs in Takayasu Arteritis

    OpenAIRE

    Clement, Marc; Galy, Adrien; Bruneval, Patrick; Morvan, Marion; Hyafil, Fabien; Benali, Khadija; Pasi, Nicoletta; Deschamps, Lydia; Pellenc, Quentin; Papo, Thomas; Nicoletti, Antonino; Sacre, Karim

    2016-01-01

    Objective The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Methods Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune ce...

  13. Phenotypes and functions of persistent Sendai virus-induced antibody forming cells and CD8+ T cells in diffuse nasal-associated lymphoid tissue typify lymphocyte responses of the gut.

    Science.gov (United States)

    Rudraraju, Rajeev; Surman, Sherri; Jones, Bart; Sealy, Robert; Woodland, David L; Hurwitz, Julia L

    2011-02-20

    Lymphocytes of the diffuse nasal-associated lymphoid tissue (d-NALT) are uniquely positioned to tackle respiratory pathogens at their point-of-entry, yet are rarely examined after intranasal (i.n.) vaccinations or infections. Here we evaluate an i.n. inoculation with Sendai virus (SeV) for elicitation of virus-specific antibody forming cells (AFCs) and CD8(+) T cells in the d-NALT. Virus-specific AFCs and CD8(+) T cells each appeared by day 7 after SeV inoculation and persisted for 8 months, explaining the long-sustained protection against respiratory virus challenge conferred by this vaccine. AFCs produced IgM, IgG1, IgG2a, IgG2b and IgA, while CD8+ T cells were cytolytic and produced low levels of cytokines. Phenotypic analyses of virus-specific T cells revealed striking similarities with pathogen-specific immune responses in the intestine, highlighting some key features of adaptive immunity at a mucosal site. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Suitability of stratagene reference RNA for analysis of lymphoid tissues

    DEFF Research Database (Denmark)

    Dybkaer, Karen; Zhou, Guimei; Iqbal, Javeed

    2004-01-01

    acceptable gene coverage to serve as a comprehensive standard for gene expression profiling of lymphoid tissues. Our lymphoid standard was prepared from thymus, spleen, tonsil, and cell lines representing immature B cells, plasma cells, and natural killer (NK) cells, thus covering the entire spectrum...... of lymphoid cells and most stromal elements present in specialized lymphoid tissues. The two standards were co-hybridized on oligonucleotide microarrays containing 17,260 genes, and both had fluorescence intensities above background for approximately 85% of the genes. Despite the limited representation...... of lymphoid cells in the Stratagene standard, only 4.2% genes exhibited expression differences greater than 2-fold including only 0.35% with differences greater than 4-fold. Although the lymphoid standard reflected a more comprehensive representation of immune system-associated genes, the Stratagene standard...

  15. Di (2-ethylhexyl Phthalate Exposure Impairs Growth of Antral Follicle in Mice.

    Directory of Open Access Journals (Sweden)

    Lan Li

    Full Text Available Di (2-ethylhexyl phthalate (DEHP is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 μg/kg DEHP every 5 days from postnatal day 0 (0 dpp to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and γH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox-sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre-pubertal stage in mice.

  16. Modelling hair follicle growth dynamics as an excitable medium.

    Directory of Open Access Journals (Sweden)

    Philip J Murray

    Full Text Available The hair follicle system represents a tractable model for the study of stem cell behaviour in regenerative adult epithelial tissue. However, although there are numerous spatial scales of observation (molecular, cellular, follicle and multi follicle, it is not yet clear what mechanisms underpin the follicle growth cycle. In this study we seek to address this problem by describing how the growth dynamics of a large population of follicles can be treated as a classical excitable medium. Defining caricature interactions at the molecular scale and treating a single follicle as a functional unit, a minimal model is proposed in which the follicle growth cycle is an emergent phenomenon. Expressions are derived, in terms of parameters representing molecular regulation, for the time spent in the different functional phases of the cycle, a formalism that allows the model to be directly compared with a previous cellular automaton model and experimental measurements made at the single follicle scale. A multi follicle model is constructed and numerical simulations are used to demonstrate excellent qualitative agreement with a range of experimental observations. Notably, the excitable medium equations exhibit a wider family of solutions than the previous work and we demonstrate how parameter changes representing altered molecular regulation can explain perturbed patterns in Wnt over-expression and BMP down-regulation mouse models. Further experimental scenarios that could be used to test the fundamental premise of the model are suggested. The key conclusion from our work is that positive and negative regulatory interactions between activators and inhibitors can give rise to a range of experimentally observed phenomena at the follicle and multi follicle spatial scales and, as such, could represent a core mechanism underlying hair follicle growth.

  17. Detection of DNA damage in oocytes of small ovarian follicles following phosphoramide mustard exposures of cultured rodent ovaries in vitro

    International Nuclear Information System (INIS)

    Petrillo, Stephanie K.; Desmeules, Patrice; Truong, To-Quyen; Devine, Patrick J.

    2011-01-01

    Healthy oocytes are critical for producing healthy children, but little is known about whether or not oocytes have the capacity to identify and recover from injury. Using a model ovotoxic alkylating drug, cyclophosphamide (CPA), and its active metabolite, phosphoramide mustard (PM), we previously showed that PM (≥ 3 μM) caused significant follicle loss in postnatal day 4 (PND4) mouse ovaries in vitro. We now investigate whether PM induces DNA damage in oocytes, examining histone H2AX phosphorylation (γH2AX), a marker of DNA double-strand breaks (DSBs). Exposure of cultured PND4 mouse ovaries to 3 and 0.1 μM PM induced significant losses of primordial and small primary follicles, respectively. PM-induced γH2AX was observed predominantly in oocytes, in which foci of γH2AX staining increased in a concentration-dependent manner and peaked 18-24 h after exposure to 3-10 μM PM. Numbers of oocytes with ≥ 5 γH2AX foci were significantly increased both 1 and 8 days after exposure to ≥ 1 μM PM compared to controls. Inhibiting the kinases that phosphorylate H2AX significantly increased follicle loss relative to PM alone. In adult mice, CPA also induced follicle loss in vivo. PM also significantly decreased primordial follicle numbers (≥ 30 μM) and increased γH2AX foci (≥ 3 μM) in cultured PND4 Sprague-Dawley rat ovaries. Results suggest oocytes can detect PM-induced damage at or below concentrations which cause significant follicle loss, and there are quantitative species-specific differences in sensitivity. Surviving oocytes with DNA damage may represent an increased risk for fertility problems or unhealthy offspring.

  18. B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue

    OpenAIRE

    Carlsen, H S; Baekkevold, E S; Johansen, F-E; Haraldsen, G; Brandtzaeg, P

    2002-01-01

    Background and aims: In mice, the B lymphocyte chemoattractant (BLC) CXC chemokine ligand 13 (CXCL13) is sufficient to induce a series of events leading to the formation of organised lymphoid tissue. Its receptor, CXCR5, is required for normal development of secondary lymphoid tissue. However, the human counterpart, B cell attracting chemokine 1 (BCA-1) has only been detected in the stomach and appendix and not in other parts of normal or diseased gut. Hence to elucidate the potential role of...

  19. Alginate: A Versatile Biomaterial to Encapsulate Isolated Ovarian Follicles.

    Science.gov (United States)

    Vanacker, Julie; Amorim, Christiani A

    2017-07-01

    In vitro culture of ovarian follicles isolated or enclosed in ovarian tissue fragments and grafting of isolated ovarian follicles represent a potential alternative to restore fertility in cancer patients who cannot undergo cryopreservation of embryos or oocytes or transplantation of frozen-thawed ovarian tissue. In this regard, respecting the three-dimensional (3D) architecture of isolated follicles is crucial to maintaining their proper follicular physiology. To this end, alginate hydrogel has been widely investigated using follicles from numerous animal species, yielding promising results. The goal of this review is therefore to provide an overview of alginate applications utilizing the biomaterial as a scaffold for 3D encapsulation of isolated ovarian follicles. Different methods of isolated follicle encapsulation in alginate are discussed in this review, as its use of 3D alginate culture systems as a tool for in vitro follicle analysis. Possible improvements of this matrix, namely modification with arginine-glycine-aspartic acid peptide or combination with fibrin, are also summarized. Encouraging results have been obtained in different animal models, and particularly with isolated follicles encapsulated in alginate matrices and grafted to mice. This summary is designed to guide the reader towards development of next-generation alginate scaffolds, with enhanced properties for follicle encapsulation.

  20. Hallmarks of Human Small Antral Follicle Development

    DEFF Research Database (Denmark)

    Kristensen, Stine G; Mamsen, Linn S; Jeppesen, Janni V

    2018-01-01

    Regulation of human ovarian steroidogenesis differs from other species and precise knowledge on how human small antral follicles (hSAF) develop and acquire competence for continued growth and steroid output is still incomplete. The present study has characterized almost 1,000 normal hSAF collected...... increased steroid output profoundly. Furthermore, the highly significant association between FSHR and AR mRNA gene expression enforces important functions of androgens in follicular development. Collectively, these data reintroduce the understanding of the follicular phase as two parted in which regulation...

  1. Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

    Science.gov (United States)

    Everaere, Laetitia; Ait-Yahia, Saliha; Molendi-Coste, Olivier; Vorng, Han; Quemener, Sandrine; LeVu, Pauline; Fleury, Sebastien; Bouchaert, Emmanuel; Fan, Ying; Duez, Catherine; de Nadai, Patricia; Staels, Bart; Dombrowicz, David; Tsicopoulos, Anne

    2016-11-01

    Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity. Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T H 2 and T H 17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T H 2 and T H 17 infiltration. These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Peripheral tissue homing receptor control of naïve, effector, and memory CD8 T cell localization in lymphoid and non-lymphoid tissues.

    Science.gov (United States)

    Brinkman, C Colin; Peske, J David; Engelhard, Victor Henry

    2013-01-01

    T cell activation induces homing receptors that bind ligands on peripheral tissue vasculature, programing movement to sites of infection and injury. There are three major types of CD8 effector T cells based on homing receptor expression, which arise in distinct lymphoid organs. Recent publications indicate that naïve, effector, and memory T cell migration is more complex than once thought; while many effectors enter peripheral tissues, some re-enter lymph nodes (LN), and contain central memory precursors. LN re-entry can depend on CD62L or peripheral tissue homing receptors. Memory T cells in LN tend to express the same homing receptors as their forebears, but often are CD62Lneg. Homing receptors also control CD8 T cell tumor entry. Tumor vasculature has low levels of many peripheral tissue homing receptor ligands, but portions of it resemble high endothelial venules (HEV), enabling naïve T cell entry, activation, and subsequent effector activity. This vasculature is associated with positive prognoses in humans, suggesting it may sustain ongoing anti-tumor responses. These findings reveal new roles for homing receptors expressed by naïve, effector, and memory CD8 T cells in controlling entry into lymphoid and non-lymphoid tissues.

  3. The Development of Adult Innate Lymphoid Cells

    Science.gov (United States)

    Yang, Qi; Bhandoola, Avinash

    2016-01-01

    Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

  4. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring.

    Directory of Open Access Journals (Sweden)

    Angelica B Bernal

    Full Text Available BACKGROUND: We have shown recently that maternal undernutrition (UN advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of

  5. Cell cycle evaluation of granulosa cells in the {gamma}-irradiated mouse ovarian follicles

    Energy Technology Data Exchange (ETDEWEB)

    KIm, Jin Kyu; Lee, Chang Joo; Lee, Young Keun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Song, Kang Won; Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    1999-03-01

    This study was carried out to evaluate the biochemical and morphological effects of ionizing radiation on mouse ovarian follicles. Immature mice (ICR, 3 week-old) were irradiated with a dose of LD{sub 80(30)} at KAERI. The ovaries were collected after 6 hours, 12 hours, 1 day, and 2 days post irradiation. With the morphological basis of the histological staining with hematoxylin-eosin, immunohistochemical preparation using in situ 3'-end labeling was evaluated. Flow cytometric evaluation of DNA extracted from the whole ovary was performed. The percentage of A{sub 0} (subpopulation of cells with degraded DNA and with lower DNA fluorescence than G{sub 0}/G{sub 1} cells), apoptotic, cells in the cell cycle was significantly higher in the irradiated group than in the control group. The number of in situ 3'-end labeled follicles increased at 6 hours post irradiation. All the analyses represented that the ionizing radiation-induced follicular atresia was taken place via an apoptotic degeneration. Such a degeneration underwent very fast and acutely. Therefore, it is concluded that the radiation-induced follicular degeneration is, like the spontaneous atresia, mediated by an acute apoptosis of follicular granulosa cells. Flow cytometric evaluation of cell cycles can make the role for quantifying the atretic follicles and understanding the mechanism of the radiation-induced cell death.

  6. Transcriptome Analysis on Single Small Yellow Follicles Reveals That Wnt4 Is Involved in Chicken Follicle Selection

    Directory of Open Access Journals (Sweden)

    Yiya Wang

    2017-11-01

    Full Text Available Ovarian follicle selection is an important process impacting the laying performance and fecundity of hens, and is regulated by follicle-stimulating hormone (FSH through binding to its receptor [follicle-stimulating hormone receptor (FSHR]. In laying hens, the small yellow follicle (6–8 mm in diameter with the highest expression of FSHR will be recruited into the preovulatory hierarchy during ovarian follicle development. The study of molecular mechanism of chicken follicle selection is helpful for the identification of genes underlying egg-laying traits in chicken and other poultry species. Herein, the transcriptomes of chicken small yellow follicles differing in the mRNA expression of FSHR were compared, and a total of 17,993 genes were identified in 3 pairs of small yellow follicles. The Wnt signaling pathway was significantly enriched in the follicles with the greatest fold change in FSHR expression. In this pathway, the expression level of Wnt4 mRNA was significantly upregulated with a log2(fold change of 2.12. We further investigated the expression, function, and regulation of Wnt4 during chicken follicle selection and found that Wnt4 mRNA reached its peak in small yellow follicles; Wnt4 stimulated the proliferation of follicular granulosa cells (GCs, increased the expression of StAR and CYP11A1 mRNA in prehierarchical and hierarchical follicles, increased the expression of FSHR mRNA, and decreased the expression of anti-Müllerian hormone and OCLN mRNA. Treatment with FSH significantly increased Wnt4 expression in GCs. Moreover, Wnt4 facilitated the effects of FSH on the production of progesterone (P4 and the mRNA expression of steroidogenic enzyme genes in the GCs of hierarchical follicles, but inhibited the effects of FSH in the GCs of prehierarchical follicles. Collectively, these data suggest that Wnt4 plays an important role in chicken follicle selection by stimulating GC proliferation and steroidogenesis. This study provides a

  7. A method for culturing human hair follicle cells.

    Science.gov (United States)

    Weterings, P J; Vermorken, A J; Bloemendal, H

    1981-01-01

    For the first time a method for culturing human hair follicle cells is described. The bovine eye lens capsule, a basement membrane-like structure, is used as the substrate for the cultures. In a culture medium supplemented with hydrocortisone and insulin about 70% of the original follicles will form growing colonies of diploid keratinocytes.

  8. Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-12-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. © 2014 The Authors.

  9. Epithelial–stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues

    Science.gov (United States)

    Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

    2014-01-01

    Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj—a gene encoding a transcription factor implicated in Notch signaling—in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. Subject Categories Development & Differentiation; Immunology; Signal Transduction PMID:25378482

  10. Mixed Lichenoid and Follicular T- and B-Cell Lymphoid Reaction to Red Tattoos With Monoclonal T Cells.

    Science.gov (United States)

    Zaaroura, Hiba; Bergman, Reuven

    2017-09-28

    Pseudolymphomatous reactions have been described to occur in tattoos. Most cases have exhibited T-cell predominance and polyclonal T-cell receptor gene rearrangements. One case with monoclonal IgH gene rearrangements progressed into B-cell lymphoma. Lichenoid infiltrates are commonly described but lymphoid follicles much less frequently. We report a case with mixed lichenoid and follicular T- and B-cell reaction to red tattoos. The histopathology and the immunohistochemical studies were constant with a mixed T- and B-cell pseudolymphoma, the IgH gene rearrangement study was polyclonal, but the T-cell receptor gene rearrangement study was monoclonal. The patient who responded to intralesional corticosteroid injections remains under close scrutiny.

  11. Prion pathogenesis and secondary lymphoid organs (SLO)

    Science.gov (United States)

    Mabbott, Neil A.

    2012-01-01

    Prion diseases are subacute neurodegenerative diseases that affect humans and a range of domestic and free-ranging animal species. These diseases are characterized by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. The pathology during prion disease appears to occur almost exclusively within the central nervous system. The extensive neurodegeneration which occurs ultimately leads to the death of the host. An intriguing feature of the prion diseases, when compared with other protein-misfolding diseases, is their transmissibility. Following peripheral exposure, some prion diseases accumulate to high levels within lymphoid tissues. The replication of prions within lymphoid tissue has been shown to be important for the efficient spread of disease to the brain. This article describes recent progress in our understanding of the cellular mechanisms that influence the propagation of prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. A thorough understanding of these events will lead to the identification of important targets for therapeutic intervention, or alternatively, reveal additional processes that influence disease susceptibility to peripherally-acquired prion diseases. PMID:22895090

  12. Ultrastructural observations of previtellogenic ovarian follicles of dove.

    Science.gov (United States)

    Zarnescu, Otilia

    2004-11-01

    Dove ovarian follicle is a complex structure composed of oocyte surrounded by a somatic compartment consisting of theca externa, theca interna and granulosa. The structure of ovarian follicle (1 and 2 mm) of dove was studied by electron microscopy. The granulosa was pseudostratified in the 1-mm-diameter follicles and stratified with two or three irregular rows of cells in the 2-mm-diameter follicles. In the larger follicle indentations between oocyte and granulosa cells become more numerous and the microvilli of granulosa cell elongated to form a zona radiata with similarly elongated oocyte microvilli. Lining bodies were present at the tips of granulosa microvilli and in the cortical region of the oocyte. In the oocyte cortex were observed coated pits, coated vesicles, dense tubules, multivesicular bodies and primordial yolk spheres. Primordial yolk spheres may contain lining bodies and were observed fused with dense tubules and multivesicular bodies or associated with smooth cisternae.

  13. First transplantation of isolated murine follicles in alginate.

    Science.gov (United States)

    Vanacker, Julie; Dolmans, Marie-Madeleine; Luyckx, Valérie; Donnez, Jacques; Amorim, Christiani A

    2014-01-01

    Our aim is to develop an artificial ovary allowing survival and growth of isolated follicles and ovarian cells, to restore fertility in women diagnosed with pathologies at high risk of ovarian involvement. For this, alginate beads containing isolated preantral follicles and ovarian cells were autografted to immunocompetent mice. One week after grafting, the beads were invaded by proliferating murine cells (12.1%) and capillaries. The recovery rate of follicles per graft ranged from 0% to 35.5%. Of the analyzed follicles, 77% were Ki67-positive and 81%, TUNEL-negative. Three antral follicles were also identified, evidencing their ability to grow in the matrix. Our results suggest that an artificial ovary is now conceivable, opening new perspectives to restore fertility in women.

  14. Multifraction dose response of growing and resting phase hair follicles

    International Nuclear Information System (INIS)

    Vegesna, V.; Withers, H.R.

    1987-01-01

    It has been established in both the clinic and the laboratory that there is a differentiation response to changes in dose per fraction in early and late responding tissues. To study one possible biological reason for differences in early and late responses. The authors selected one kind of cellular entity, the hair follicle, in two different phases of mitotic activity. The follicles are usually in a resting phase (7-12 wks), but mitotic activity can be initiated by plucking the club hairs. This was done on one half of the thorax and then exposing mice to doses of radiation (cesium gamma-ray). Dose responses for epilation between growing (early) and resting (late) follicles were compared for the same mouse. The fractionated response was studied by reducing the dose down to 2.5 Gy/fx. As the literature suggests, the total dose tolerated by a resting (late) follicle increased more than that for a growing (early) follicle

  15. Comparison of manual and automated measurements of monodominant follicle diameter with different follicle size in infertile patients.

    Directory of Open Access Journals (Sweden)

    Ping Pan

    Full Text Available This study evaluated the consistency of manual and automated measurements of monodominant follicle diameter with different follicle size in infertile patients. Transvaginal two-dimensional (2D ultrasound and SonoAVC (Sonography-based Automated Volume Calculation were both performed in 226 infertile patients with monodominant follicle growth. 2D diameters were separately compared with SonoAVC-generated d(V and m-d values in different follicle category, i.e. >10 to 14 mm, >14 to 18 mm, >18 to 22 mm and >22 mm. There was moderate degree of consistency between 2D diameter and SonoAVC-generated parameters regardless of follicle size. The mean differences were 0.82 mm between 2D diameter and SonoAVC-generated d(V value, and 0.22 mm between 2D diameter and SonoAVC-generated m-d value, respectively. The discrepancy of manual and automated measurements tended to increase as follicle size increased. Our study suggested that compared with manual measurement, SonoAVC might underestimate follicle size. The absolute size of a follicle affected the consistency of two techniques.

  16. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    Energy Technology Data Exchange (ETDEWEB)

    Madden, Jill A. [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Hoyer, Patricia B. [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Devine, Patrick J. [INRS—Institut Armand-Frappier Research Centre, University of Quebec, Laval, QC H7V 1B7 (Canada); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States)

    2014-05-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  17. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    International Nuclear Information System (INIS)

    Madden, Jill A.; Hoyer, Patricia B.; Devine, Patrick J.; Keating, Aileen F.

    2014-01-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT Thr308 protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  18. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits

    Directory of Open Access Journals (Sweden)

    J. Rodríguez-Castelán

    2017-01-01

    Full Text Available Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT. Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C. In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.

  19. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits.

    Science.gov (United States)

    Rodríguez-Castelán, J; Méndez-Tepepa, M; Carrillo-Portillo, Y; Anaya-Hernández, A; Rodríguez-Antolín, J; Zambrano, E; Castelán, F; Cuevas-Romero, E

    2017-01-01

    Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT). Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.

  20. Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

    Science.gov (United States)

    Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan

    2017-10-01

    Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.

  1. Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma

    Science.gov (United States)

    Pishdadian, Abbas; Varasteh, Abdol-Reza; Sankian, Mojtaba

    2012-01-01

    Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 “immune franchise.” Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma. PMID:23209480

  2. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

    Science.gov (United States)

    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+), a majority of those emigrating onto the supporting membrane were Bu-1a(-) and IgM(+). Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined.

  3. Follicle Online: an integrated database of follicle assembly, development and ovulation.

    Science.gov (United States)

    Hua, Juan; Xu, Bo; Yang, Yifan; Ban, Rongjun; Iqbal, Furhan; Cooke, Howard J; Zhang, Yuanwei; Shi, Qinghua

    2015-01-01

    Folliculogenesis is an important part of ovarian function as it provides the oocytes for female reproductive life. Characterizing genes/proteins involved in folliculogenesis is fundamental for understanding the mechanisms associated with this biological function and to cure the diseases associated with folliculogenesis. A large number of genes/proteins associated with folliculogenesis have been identified from different species. However, no dedicated public resource is currently available for folliculogenesis-related genes/proteins that are validated by experiments. Here, we are reporting a database 'Follicle Online' that provides the experimentally validated gene/protein map of the folliculogenesis in a number of species. Follicle Online is a web-based database system for storing and retrieving folliculogenesis-related experimental data. It provides detailed information for 580 genes/proteins (from 23 model organisms, including Homo sapiens, Mus musculus, Rattus norvegicus, Mesocricetus auratus, Bos Taurus, Drosophila and Xenopus laevis) that have been reported to be involved in folliculogenesis, POF (premature ovarian failure) and PCOS (polycystic ovary syndrome). The literature was manually curated from more than 43,000 published articles (till 1 March 2014). The Follicle Online database is implemented in PHP + MySQL + JavaScript and this user-friendly web application provides access to the stored data. In summary, we have developed a centralized database that provides users with comprehensive information about genes/proteins involved in folliculogenesis. This database can be accessed freely and all the stored data can be viewed without any registration. Database URL: http://mcg.ustc.edu.cn/sdap1/follicle/index.php © The Author(s) 2015. Published by Oxford University Press.

  4. Regulation and regulatory role of WNT signaling in potentiating FSH action during bovine dominant follicle selection.

    Directory of Open Access Journals (Sweden)

    P S P Gupta

    Full Text Available Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest and F2 (second largest follicles isolated at predeviation (PD and onset of diameter deviation (OD stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM, PD, OD and early dominance (ED stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

  5. Kidney allograft survival in dogs treated with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Howard, R.J.; Sutherland, D.E.R.; Lum, C.T.; Lewis, W.I.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1981-01-01

    Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogenic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950 to 3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned for a mean +- (SE) of 4.7 +- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15 to 76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients

  6. Participation of Mitogen-activated Protein Kinase in Luteinizing Hormone-induced Differential Regulation of Steroidogenesis and Steroidogenic Gene Expression in Mural and Cumulus Granulosa Cells of Mouse Preovulatory Follicles

    DEFF Research Database (Denmark)

    Su, You-Qiang; Nyegaard, Mette; Overgaard, Michael Toft

    2006-01-01

    changes of circulating estradiol (E2) and progesterone (P4) levels after administration of hCG. In vitro, when MGCs and COCs were treated with U0126, a specific inhibitor of MAPK3/1 activation, gonadotropin- or 8-Br-cAMP-induced P4 production, as well as expression of Star and Cyp11a1 mRNA, were...

  7. Immunohistochemical localization of basement membrane components during hair follicle morphogenesis

    DEFF Research Database (Denmark)

    Westgate, G E; Shaw, D A; Harrap, G J

    1984-01-01

    Specific antisera were used to investigate the distributions of several basement membrane zone (BMZ) components, namely, bullous pemphigoid antigen (BPA), heparan sulfate proteoglycan (HSPG), laminin, and type IV collagen, during the development of hair follicles in late embryo rats. BPA was not ......Specific antisera were used to investigate the distributions of several basement membrane zone (BMZ) components, namely, bullous pemphigoid antigen (BPA), heparan sulfate proteoglycan (HSPG), laminin, and type IV collagen, during the development of hair follicles in late embryo rats. BPA...... of the elongating follicle. HSPG was associated with the basal cell layer prior to the appearance of hair follicle primordia and became BMZ-associated before birth but after follicle buds were first observed. HSPG was also found to be associated with the basal cell surfaces in the epidermis, but not in the hair...... follicle. Laminin and type IV collagen were continually present in epidermal and follicular BMZ both before and during development of hair follicles and were later present in the dermal papilla matrix. From these observations we conclude that (1) laminin and type IV collagen are functionally important...

  8. Radiation effects on cultured human lymphoid cells

    International Nuclear Information System (INIS)

    Johansson, L.; Nilsson, K.; Carlsson, J.; Larsson, B.; Jakobsson, P.

    1981-01-01

    The cloning efficiency of human normal and malignant lymphoid cells is usually low. Radiation effects in vitro on such cells can therefore not be analysed with conventional cloning. However, this problem can be circumscribed by using the growth extrapolation method. A panel of human leukemia-lymphoma cell-lines representing Epstein-Barr virus carrying lymphoblastoid cells of presumed non-neoplastic derivation and neoplastic T- and B-lymphocytes was used to test the efficiency of this method. The sensitivity to radiation could be determined for all these cell types. The growth extrapolation method gave generally the same result as conventional cloning demonstrated by comparison with one exceptional cell-line with capacity for cloning in agar. The sensitivity varied largely between the different cell types. A common feature was that none of the cell lines had a good capacity to accumulate sublethal radiation injury. (Auth.)

  9. Innate lymphoid cells and the MHC.

    Science.gov (United States)

    Robinette, M L; Colonna, M

    2016-01-01

    Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Deciphering the Innate Lymphoid Cell Transcriptional Program

    Directory of Open Access Journals (Sweden)

    Cyril Seillet

    2016-10-01

    Full Text Available Innate lymphoid cells (ILCs are enriched at mucosal surfaces, where they provide immune surveillance. All ILC subsets develop from a common progenitor that gives rise to pre-committed progenitors for each of the ILC lineages. Currently, the temporal control of gene expression that guides the emergence of these progenitors is poorly understood. We used global transcriptional mapping to analyze gene expression in different ILC progenitors. We identified PD-1 to be specifically expressed in PLZF+ ILCp and revealed that the timing and order of expression of the transcription factors NFIL3, ID2, and TCF-1 was critical. Importantly, induction of ILC lineage commitment required only transient expression of NFIL3 prior to ID2 and TCF-1 expression. These findings highlight the importance of the temporal program that permits commitment of progenitors to the ILC lineage, and they expand our understanding of the core transcriptional program by identifying potential regulators of ILC development.

  11. Clinical epidemiological aspects of chronic lymphoid leukaemia

    International Nuclear Information System (INIS)

    Rodriguez Brunet, Marisol; Hernandez Galano, Geldris P; Suarez Beyries, Lidia C; Duverger Magdaleon, Ernesto

    2011-01-01

    A descriptive and retrospective study of 71 patients with chronic lymphoid leukemia, attended at the Hematology Service from 'Dr Juan Bruno Zayas Alfonso' Teaching General Hospital in Santiago de Cuba was carried out from January, 2001 to November, 2006, in order to identify some clinical epidemiological variables on them, to show the therapeutical variables more used, as well as to assess survival, mortality, and the main causes of the clinical entity. Elderly, male sex, and high risk category related to advanced stage were predominant in the series. The therapeutical schedule of chlorambucil and prednisone was the most used, achieving good results in the majority of the case material. The survival of patients, in general, ranged among 1-5 years, whereas deaths occurred due to disease progression, infectious respiratory processes, pro-lymphocytic transformation, second neoplasias, and strokes. (author)

  12. High-resolution CT of lymphoid interstitial pneumonia

    International Nuclear Information System (INIS)

    Vilgrain, V.; Frija, J.; Yana, C.; Couderc, L.J.; David, M.; Clauvel, J.P.; Laval-Jeantet, M.

    1989-01-01

    Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, 'ground-glass' opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient presents with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia [fr

  13. Type two innate lymphoid cells; the Janus cells in health and disease

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-01-01

    Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

  14. Type two innate lymphoid cells: the Janus cells in health and disease.

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-07-01

    Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. (Department of Biochemistry, Albany Medical College, New York, NY (USA))

    1991-06-01

    We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

  16. Effect of age and sex on fiber and follicle characteristics of an Iranian ...

    African Journals Online (AJOL)

    All the hair follicles were surrounded by associated structures such as the sweat and sebaceous glands and arrector pili muscles and located only in papillary layer of the dermis. The most common number of the secondary hair follicles in compound hair follicles was 4. The histology of all fibers and follicles in various skin ...

  17. Serial cultivation of human scalp hair follicle keratinocytes.

    Science.gov (United States)

    Weterings, P J; Roelofs, H M; Vermorken, A J; Bloemendal, H

    1983-01-01

    A method is described for the serial cultivation of adult human hair follicle keratinocytes. Plucked scalp hair follicles, placed on bovine eye lens capsules as a growth substrate, give rise to quickly expanding colonies within a few days. After trypsinization, the cells are replated with irradiated 3T3 cells as 'feeders'. Using this combination of techniques the keratinocytes can be subcultured up to four times. In this way about 10(7) keratinocytes can be generated from one single hair follicle. Moreover, the technique enables cryogenic storage of the cells, allowing for instance, convenient transportation. Subcultured hair follicle keratinocytes can be plated on glass coverslips. This allows immunofluorescence studies. The keratin cytoskeletons visualized using an antiserum against human keratin.

  18. Differentiation of human scalp hair follicle keratinocytes in culture.

    Science.gov (United States)

    Weterings, P J; Verhagen, H; Wirtz, P; Vermorken, A J

    1984-01-01

    The morphology of human scalp hair follicle keratinocytes, cultured on the bovine eye lens capsule, is studied by light and electron microscopy. The hair follicle keratinocytes in the stratified cultures are characterized by the presence of numerous tonofilaments, desmosomes and lysosomes and by the presence of glycogen accumulations. The cells in the upper layers develop a cornified envelope. Moreover, an incomplete basal lamina is found between the capsule and the basal cells. However, some features of epidermal keratinocytes in vivo, such as keratohyalin granules and stratum corneum formation, are absent. Analysis of the polypeptides by sodium dodecylsulfate polyacrylamide gel electrophoresis also reveals differences between the cultured hair follicle cells and epidermis, whilst the patterns of cultured cells and hair follicle sheaths are similar. The morphological and protein biosynthetic aspects of terminal differentiation of the keratinocytes in vitro are correlated. These results are discussed in the light of the findings with cultured epidermal keratinocytes, reported in the literature.

  19. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress

    International Nuclear Information System (INIS)

    Sobinoff, A.P.; Pye, V.; Nixon, B.; Roman, S.D.; McLaughlin, E.A.

    2012-01-01

    Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemical analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.

  20. Mouse preantral follicle growth in 3D co-culture system using human menstrual blood mesenchymal stem cell.

    Science.gov (United States)

    Rajabi, Zahra; Yazdekhasti, Hossein; Noori Mugahi, Seyed Mohammad Hossein; Abbasi, Mehdi; Kazemnejad, Somaieh; Shirazi, Abolfazl; Majidi, Masoumeh; Zarnani, Amir-Hassan

    2018-03-01

    Follicle culture provides a condition which can help investigators to evaluate various aspects of ovarian follicle growth and development and impact of different components and supplementations as well as presumably application of follicle culture approach in fertility preservation procedures. Mesenchymal Stem Cells (MSCs), particularly those isolated from menstrual blood has the potential to be used as a tool for improvement of fertility. In the current study, a 3D co-culture system with mice preantral follicles and human Menstrual Blood Mesenchymal Stem Cells (MenSCs) using either collagen or alginate beads was designed to investigate whether this system allows better preantral follicles growth and development. Results showed that MenSCs increase the indices of follicular growth including survival rate, diameter, and antrum formation as well as the rate of in vitro maturation (IVM) in both collagen and alginates beads. Although statistically not significant, alginate was found to be superior in terms of supporting survival rate and antrum formation. Hormone assay demonstrated that the amount of secreted 17 β-estradiol and progesterone in both 3D systems increased dramatically after 12 days, with the highest levels in system employing MenSCs. Data also demonstrated that relative expression of studied genes increased for Bmp15 and Gdf9 and decreased for Mater when follicles were cultured in the presence of MenSCs. Collectively, results of the present study showed that MenSCs could improve indices of follicular growth and maturation in vitro. Further studies are needed before a clinical application of MenSCs-induced IVM is considered. Copyright © 2018 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. All rights reserved.

  1. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Sobinoff, A.P.; Pye, V. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); Nixon, B.; Roman, S.D. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Callaghan, NSW2308 (Australia); McLaughlin, E.A., E-mail: eileen.mclaughlin@newcastle.edu.au [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Callaghan, NSW2308 (Australia)

    2012-04-01

    Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemical analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.

  2. Proliferating Cell Nuclear Antigen (PCNA) Regulates Primordial Follicle Assembly by Promoting Apoptosis of Oocytes in Fetal and Neonatal Mouse Ovaries

    Science.gov (United States)

    Zhang, Yuanwei; Jiang, Xiaohua; Zhang, Huan; Ma, Tieliang; Zheng, Wei; Sun, Rui; Shen, Wei; Sha, Jiahao; Cooke, Howard J.; Shi, Qinghua

    2011-01-01

    Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA), a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer guanulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries. PMID:21253613

  3. Proliferating cell nuclear antigen (PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries.

    Directory of Open Access Journals (Sweden)

    Bo Xu

    Full Text Available Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA, a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer granulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries.

  4. Bioengineering of Artificial Antigen Presenting Cells and Lymphoid Organs.

    Science.gov (United States)

    Wang, Chao; Sun, Wujin; Ye, Yanqi; Bomba, Hunter N; Gu, Zhen

    2017-01-01

    The immune system protects the body against a wide range of infectious diseases and cancer by leveraging the efficiency of immune cells and lymphoid organs. Over the past decade, immune cell/organ therapies based on the manipulation, infusion, and implantation of autologous or allogeneic immune cells/organs into patients have been widely tested and have made great progress in clinical applications. Despite these advances, therapy with natural immune cells or lymphoid organs is relatively expensive and time-consuming. Alternatively, biomimetic materials and strategies have been applied to develop artificial immune cells and lymphoid organs, which have attracted considerable attentions. In this review, we survey the latest studies on engineering biomimetic materials for immunotherapy, focusing on the perspectives of bioengineering artificial antigen presenting cells and lymphoid organs. The opportunities and challenges of this field are also discussed.

  5. Morphology of mucosa-associated lymphoid tissue in odontocetes.

    Science.gov (United States)

    Silva, Fernanda M O; Guimarães, Juliana P; Vergara-Parente, Jociery E; Carvalho, Vitor L; Carolina, Ana; Meirelles, O; Marmontel, Miriam; Oliveira, Bruno S S P; Santos, Silvanise M; Becegato, Estella Z; Evangelista, Janaina S A M; Miglino, Maria Angelica

    2016-09-01

    This study describes the mucosa-associated lymphoid tissue (MALT) in odontocetes from the Brazilian coast and freshwater systems. Seven species were evaluated and tissue samples were analyzed by light, scanning and transmission electron microscopy, and immunohistochemistry. Laryngeal tonsil was a palpable oval mass located in the larynx, composed of a lymphoepithelial complex. Dense collections of lymphocytes were found in the skin of male fetus and calf. Clusters of lymphoid tissue were found in the uterine cervix of a reproductively active juvenile female and along the pulmonary artery of an adult female. Lymphoid tissues associated with the gastrointestinal tract were characterized by diffusely arranged or organized lymphocytes. The anal tonsil was composed of an aggregate of lymphoid tissue occurring exclusively in the anal canal, being composed of squamous epithelium branches. MALT was present in different tissues and organic systems of cetaceans, providing constant protection against mucosal pathogens present in their environment. © 2016 Wiley Periodicals, Inc.

  6. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    International Nuclear Information System (INIS)

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B.

    1991-01-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy

  7. Alterations in Hair Follicle Dynamics in Women

    Directory of Open Access Journals (Sweden)

    Claudine Piérard-Franchimont

    2013-01-01

    Full Text Available Endocrine changes supervening after parturition and menopause participate in the control of sebum production and hair growth modulation. The ensuing conditions include some peculiar aspects of hair loss (effluvium, alopecia, and facial hirsutism. The hair cycling is of major clinical relevance because most hair growth disorders result from disturbances in this chronobiological feature. Of note, any correlation between a biologic abnormality and hair cycling disturbance does not prove a relationship of causality. The proportion of postmenopausal women is rising in the overall population. Therefore, the prevalence of these hair follicle disturbances is globally on the rise. Current therapies aim at correcting the underlying hormonal imbalances, and at improving the overall cosmetic appearance. However, in absence of pathogenic diagnosis and causality criteria, chances are low that a treatment given by the whims of fate will adequately control hair effluvium. The risk and frequency of therapeutic inertia are further increased. When the hair loss is not controlled and/or compensated by growth of new hairs, several clinical aspects of alopecia inexorably develop. Currently, there is little evidence supporting any specific treatment for these endocrine hair disorders in post-partum and postmenopausal women. Current hair treatment strategies are symptomatic and nonspecific so current researchers aim at developing new, targeted methods.

  8. Variation in ovarian follicle density during human fetal development.

    Science.gov (United States)

    Geber, Selmo; Megale, Rodrigo; Vale, Fabiene; Lanna, Ana Maria Arruda; Cabral, Antônio Carlos Vieira

    2012-09-01

    To obtain a precise estimate of ovarian follicle density and variation in the number of follicles at several gestational ages during human fetal development. Twelve necropsied ovaries from 9 fetuses (gestational age: 24 to 36 weeks) and 3 neonates (who died within the first hours of life) were studied. Ovaries were fixed with 4 % formaldehyde and embedded in paraffin. Serial, 7 mm thick sections of the ovaries were cut and evaluated at every 50 cuts. Follicles were counted in 10 regions (each measuring 625 μm(2)) of the ovarian cortex and the number of follicles per mm³ was calculated. The number of follicles per 0.25 mm² ranged from 10.9 (± 4.8) in a neonate to 34.7 (± 10.6) also in a neonate. Among fetuses, follicle density was lowest at 36 weeks of gestation (11.1 ± 6.2) and highest at 26 weeks (32 ± 8.9). The total number of follicles ranged from 500,000 at the age of 22 weeks to > 1,000,000 at the age of 39 weeks. Our results show a peak in the number of follicles during intrauterine life at approximately 26 weeks, followed by a rapid reduction in this number before birth, providing a step forward towards the understanding of primordial follicular assembly in humans and, ultimately, the identification of the determinants of reproductive capacity.

  9. Multiple calcifying hyperplastic dental follicles: A case report

    International Nuclear Information System (INIS)

    Aydin, Ulkem; Baykul, Timucin; Yildirim, Benay; Yildirim, Derya; Bozdemir, Esin; Karaduman, Ayse

    2013-01-01

    This report describes a 31-year-old female patient with six impacted teeth. The crowns of the impacted teeth were surrounded with cyst-like lesions with a mixed internal structure and well-defined cortical borders. Microscopic examination of the specimen obtained from the follicle of the left mandibular third molar tooth revealed loose to moderately dense collagenous connective tissue with abundant calcified material and sparse epithelial islands. A diagnosis of multiple calcifying hyperplastic dental follicles was made.

  10. Multiple calcifying hyperplastic dental follicles: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Aydin, Ulkem [Dept. of Dentomaxillofacial Radiology, Baskent University Faculty of Dentistry, Ankara (Turkey); Baykul, Timucin [Dept. of Oral and Maxillofacial Surgery, Suleyman Demirel University Faculty of Dentistry, Isparta (Turkey); Yildirim, Benay [Dept. of Oral Pathology, Gazi University Faculty of Dentistry, Ankara (Turkey); Yildirim, Derya; Bozdemir, Esin [Dept. of Dentomaxillofacial Radiology, Suleyman Demirel University Faculty of Dentistry, Isparta (Turkey); Karaduman, Ayse [Atlas Dent Dental Health Center, Aydin (Turkey)

    2013-12-15

    This report describes a 31-year-old female patient with six impacted teeth. The crowns of the impacted teeth were surrounded with cyst-like lesions with a mixed internal structure and well-defined cortical borders. Microscopic examination of the specimen obtained from the follicle of the left mandibular third molar tooth revealed loose to moderately dense collagenous connective tissue with abundant calcified material and sparse epithelial islands. A diagnosis of multiple calcifying hyperplastic dental follicles was made.

  11. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2015-01-01

    Full Text Available Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1 or fibroblasts (FB, group 2 under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P<0.001 without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

  12. Culture of bovine ovarian follicle wall sections maintained the highly estrogenic profile under basal and chemically defined conditions

    International Nuclear Information System (INIS)

    Vasconcelos, R.B.; Salles, L.P.; Silva, I. Oliveira e; Gulart, L.V.M.; Souza, D.K.; Torres, F.A.G.; Bocca, A.L.; Silva, A.A.M. Rosa e

    2013-01-01

    Follicle cultures reproduce in vitro the functional features observed in vivo. In a search for an ideal model, we cultured bovine antral follicle wall sections (FWS) in a serum-free defined medium (DM) known to induce 17β-estradiol (E 2 ) production, and in a nondefined medium (NDM) containing serum. Follicles were sectioned and cultured in NDM or DM for 24 or 48 h. Morphological features were determined by light microscopy. Gene expression of steroidogenic enzymes and follicle-stimulating hormone (FSH) receptor were determined by RT-PCR; progesterone (P 4 ) and E 2 concentrations in the media were measured by radioimmunoassay. DM, but not NDM, maintained an FWS morphology in vitro that was similar to fresh tissue. DM also induced an increase in the expression of all steroidogenic enzymes, except FSH receptor, but NDM did not. In both DM and NDM, there was a gradual increase in P 4 throughout the culture period; however, P 4 concentration was significantly higher in NDM. In both media, E 2 concentration was increased at 24 h, followed by a decrease at 48 h. The E 2 :P 4 ratio was higher in DM than in NDM. These results suggest that DM maintains morphological structure, upregulates the expression of steroidogenic enzyme genes, and maintains steroid production with a high E 2 :P 4 ratio in FWS cultures

  13. Culture of bovine ovarian follicle wall sections maintained the highly estrogenic profile under basal and chemically defined conditions

    Energy Technology Data Exchange (ETDEWEB)

    Vasconcelos, R.B. [Laboratório de Biotecnologia da Reprodução, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Salles, L.P. [Laboratório de Biologia Molecular, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Silva, I. Oliveira e; Gulart, L.V.M. [Laboratório de Biotecnologia da Reprodução, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Souza, D.K. [Laboratório de Biotecnologia da Reprodução, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Faculdade de Ceilândia, Universidade de Brasília, Ceilândia, DF (Brazil); Torres, F.A.G. [Laboratório de Biologia Molecular, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Bocca, A.L. [Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil); Silva, A.A.M. Rosa e [Laboratório de Biotecnologia da Reprodução, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF (Brazil)

    2013-08-16

    Follicle cultures reproduce in vitro the functional features observed in vivo. In a search for an ideal model, we cultured bovine antral follicle wall sections (FWS) in a serum-free defined medium (DM) known to induce 17β-estradiol (E{sub 2}) production, and in a nondefined medium (NDM) containing serum. Follicles were sectioned and cultured in NDM or DM for 24 or 48 h. Morphological features were determined by light microscopy. Gene expression of steroidogenic enzymes and follicle-stimulating hormone (FSH) receptor were determined by RT-PCR; progesterone (P{sub 4}) and E{sub 2} concentrations in the media were measured by radioimmunoassay. DM, but not NDM, maintained an FWS morphology in vitro that was similar to fresh tissue. DM also induced an increase in the expression of all steroidogenic enzymes, except FSH receptor, but NDM did not. In both DM and NDM, there was a gradual increase in P{sub 4} throughout the culture period; however, P{sub 4} concentration was significantly higher in NDM. In both media, E{sub 2} concentration was increased at 24 h, followed by a decrease at 48 h. The E{sub 2}:P{sub 4} ratio was higher in DM than in NDM. These results suggest that DM maintains morphological structure, upregulates the expression of steroidogenic enzyme genes, and maintains steroid production with a high E{sub 2}:P{sub 4} ratio in FWS cultures.

  14. Early lymphoid lesions: conceptual, diagnostic and clinical challenges

    OpenAIRE

    Ganapathi, Karthik A.; Pittaluga, Stefania; Odejide, Oreofe O.; Freedman, Arnold S.; Jaffe, Elaine S.

    2014-01-01

    There are no “benign lymphomas”, a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. Thus, benign clonal expansions of lymphocytes are only rarely recognized when localized. Recent studies have identified a number of lymphoid proliferations that lie at the interface between benign and malignant. Some of these are clonal proliferations that carry many of the molecular hallmarks of their malignant counterparts, such as BCL2/IGH and CCND1/IGH transl...

  15. Innate lymphoid cells at the interface between obesity and asthma.

    Science.gov (United States)

    Everaere, Laetitia; Ait Yahia, Saliha; Bouté, Mélodie; Audousset, Camille; Chenivesse, Cécile; Tsicopoulos, Anne

    2018-01-01

    Obesity and asthma prevalence has dramatically and concomitantly increased over the last 25 years, and many epidemiological studies have highlighted obesity as an important risk factor for asthma. Although many studies have been performed, the underlying mechanisms remain poorly understood. Innate mechanisms have been involved in both diseases, in particular through the recently described innate lymphoid cells (ILCs). ILCs are subdivided into three groups that are defined by their cytokine production and by their master transcription factor expression, in sharp correlation with their T helper counterparts. However, unlike T helper cells, ILCs do not express antigen-specific receptors, but respond to damage-induced signals. ILCs have been found in target tissues of both diseases, and data have implicated these cells in the pathogenesis of both diseases. In particular group 2 ILCs (ILC2) are activated in both the adipose and lung tissues under the effect of interleukin-33 and interleukin-25 expression. However, counter-intuitively to the well-known association between obesity and asthma, ILC2 are beneficial for obesity but deleterious for asthma. This review will examine the roles of ILCs in each disease and recent data highlighting ILCs as a putative link between obesity and asthma. © 2017 John Wiley & Sons Ltd.

  16. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

    International Nuclear Information System (INIS)

    Basavarajappa, Mallikarjuna S.; Craig, Zelieann R.; Hernandez-Ochoa, Isabel; Paulose, Tessie; Leslie, Traci C.; Flaws, Jodi A.

    2011-01-01

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E 2 ) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E 2 metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E 2 , testosterone, androstenedione, and progesterone (P 4 ) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17β-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17α-hydroxylase/17,20-lyase (Cyp17a1), 3β hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: → MXC inhibits steroidogenesis → MXC inhibits steroidogenic enzymes → MXC induces metabolic enzymes

  17. A delay differential equation model of follicle waves in women.

    Science.gov (United States)

    Panza, Nicole M; Wright, Andrew A; Selgrade, James F

    2016-01-01

    This article presents a mathematical model for hormonal regulation of the menstrual cycle which predicts the occurrence of follicle waves in normally cycling women. Several follicles of ovulatory size that develop sequentially during one menstrual cycle are referred to as follicle waves. The model consists of 13 nonlinear, delay differential equations with 51 parameters. Model simulations exhibit a unique stable periodic cycle and this menstrual cycle accurately approximates blood levels of ovarian and pituitary hormones found in the biological literature. Numerical experiments illustrate that the number of follicle waves corresponds to the number of rises in pituitary follicle stimulating hormone. Modifications of the model equations result in simulations which predict the possibility of two ovulations at different times during the same menstrual cycle and, hence, the occurrence of dizygotic twins via a phenomenon referred to as superfecundation. Sensitive parameters are identified and bifurcations in model behaviour with respect to parameter changes are discussed. Studying follicle waves may be helpful for improving female fertility and for understanding some aspects of female reproductive ageing.

  18. Mucosa-associated lymphoid tissue (MALT lymphoma of the stomach: features of pathomorphological diagnostics

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-04-01

    Full Text Available On the base of our own observations and literature data it was determined that the distinctive pathologic features of MALT-lymphoma of the stomach are the presence of a dense diffuse lymphocytic infiltrate of centrocyte-like tumor cells of marginal zone (small cells resembling centrocytes with distinct bright rim of cytoplasm, with small nuclei of irregular shape, sometimes – split, containing coarse chromatin and indistinct nucleoli in the lamina propria between the reactive lymph follicles and glands of the mucous membrane, monocytoid B-lymphocytes characterized by clear cell borders, broad light cytoplasm and bean-like nucleus, plasma cells, which may contain Dutcher bodies – intranuclear inclusions of immunoglobulins; single large centroblast-like or immunoblast-like cells having round-oval or slightly irregular in shape nuclei with 1-3 nucleoli, or vesicular-like round in shape nuclei with compact, centrally located nucleolus; small lymphocytes. Infiltration looks as tumorcell layers or, more rarely, fuzzy nodular cellular formations. An important diagnostic criterion is the presence of "lymphoepithelial lesions" zones of glands due to infiltration by 3 or more centrocyte-like tumor cell aggregates with glands’ basement membranes destruction. In the damaged glands epithelium edema and eosinophilia are marked, but if extensive infiltration is present among the lymphoid infiltrate there are only clusters of degenerated cells at the site of destroyed epithelium. Low-grade MALT-lymphoma is characterized by the absence of distinct macroscopic changes and the prevalence of "mature" tumor cells over the blasts in histological picture. MALT-lymphoma with signs of transformation into high-grade lymphoma is characterized macroscopically by distinct exophytic component, hyperplasia of folds with ulcerous defects up to 1-2 cm in diameter. Histologic picture displays a significant amount of blast cells – both in the infiltrate and in the areas

  19. The effect of acrylamide on alpha-naphthyl acetate esterase enzyme in blood circulating lymphocytes and gut associated lymphoid tissues in rats.

    Science.gov (United States)

    Yener, Y; Sur, E; Telatar, T; Oznurlu, Y

    2013-01-01

    The aim of this study is to determine the functional effects of the acrylamide (AA) administrated by oral gavage on the peripheral blood lymphocytes (PBL) and the Gut Associated Lymphoid Tissue (GALT) in male Sprague-Dawley rats using alpha-naphthyl acetate esterase (ANAE) demonstration. For this purpose, two separate experiments were performed with Sprague Dawley rats. In Experiment-I rats were gavaged with 0, 30, 45 and 60 mg/kgb.w. AA for five consecutive days and in Experiment-II rats were gavaged with 0, 125, 150, and 175 mg/kg/b.w. AA for single oral dose. Animals were sacrificed 24 h after the last treatments in both experiments by servical dislocations under ether anaesthesia. Blood samples were collected from the heart in heparinized (10 UI heparin/ml(-1) of the blood) tubes before sacrification and lymphoid tissue samples from the ileal Peyer's patches (IPPs) were taken and processed for histochemical demonstration of ANAE following the sacrification. The lymphoid follicles of the IPPs of animals given 125, 150 and 175 mg/kgb.w. AA were markedly reduced in size. Germinal centres (GCs) markedly regressed in AA-treated animals compared with those of controls. ANAE-positive lymphocyte depletion of IPPs was very prominent in the high doses AA-treated animals. In the animals treated with 30, 45, and 60 mg/kg b.w. AA, the IPPs had similar histology to those of the controls. ANAE-positive peripheral blood lymphocyte levels significantly decreased in AA exposed groups in a dose dependent manner (pAssociated Lymphoid Tissue (GALT) in rats. Copyright © 2011 Elsevier GmbH. All rights reserved.

  20. Epigenomic Views of Innate Lymphoid Cells.

    Science.gov (United States)

    Sciumè, Giuseppe; Shih, Han-Yu; Mikami, Yohei; O'Shea, John J

    2017-01-01

    The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity.

  1. Functional anatomy of the hair follicle: The Secondary Hair Germ.

    Science.gov (United States)

    Panteleyev, Andrey A

    2018-07-01

    The secondary hair germ (SHG)-a transitory structure in the lower portion of the mouse telogen hair follicle (HF)-is directly involved in anagen induction and eventual HF regrowth. Some crucial aspects of SHG functioning and ontogenetic relations with other HF parts, however, remain undefined. According to recent evidence (in contrast to previous bulge-centric views), the SHG is the primary target of anagen-inducing signalling and a source of both the outer root sheath (ORS) and ascending HF layers during the initial (morphogenetic) anagen subphase. The SHG is comprised of two functionally distinct cell populations. Its lower portion (originating from lower HF cells that survived catagen) forms all ascending HF layers, while the upper SHG (formed by bulge-derived cells) builds up the ORS. The predetermination of SHG cells to a specific morphogenetic fate contradicts their attribution to the "stem cell" category and supports SHG designation as a "germinative" or a "founder" cell population. The mechanisms of this predetermination driving transition of the SHG from "refractory" to the "competent" state during the telogen remain unknown. Functionally, the SHG serves as a barrier, protecting the quiescent bulge stem cell niche from the extensive follicular papilla/SHG signalling milieu. The formation of the SHG is a prerequisite for efficient "precommitment" of these cells and provides for easier sensing and a faster response to anagen-inducing signals. In general, the formation of the SHG is an evolutionary adaptation, which allowed the ancestors of modern Muridae to acquire a specific, highly synchronized pattern of hair cycling. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    Directory of Open Access Journals (Sweden)

    Misae Tsunaka

    2016-07-01

    Full Text Available Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma, Molt4 (acute T-lymphoblastic leukemia, and Ramos (Burkitt lymphoma were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs.

  3. Antioxidant effects of captopril against lead acetate-induced hepatic and splenic tissue toxicity in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Badr A. Aldahmash

    2016-11-01

    Full Text Available Considering that lead caused a lot of health problems in the world, the present study was carried out to investigate the protective effect of captopril as antioxidants to reduce liver and spleen toxicity induced by lead. Animals were divided into 3 groups, the 1st group served as control group, the 2nd group received 20 mg/kg of lead acetate and the 3rd group received 50 mg/kg of captopril one hour prior to lead administration for 5 days. Results showed that lead intake caused severe alterations in the liver and spleen manifested by hepatocytes degeneration, leukocytic infiltration, fibrosis in liver and moderate to severe liver pathological score. Spleen showed ill-defined architecture, presence of large macrophages and lymphoid necrosis. Administration of captopril reduced hepatotoxicity, liver fibrosis and decrease in pathological scoring system. Moreover, reduced toxicity in spleen is represented by reduction in necrotic areas, more or less healthy lymphoid follicles and decreasing in pathological scoring system. Keywords: Captopril, Mice, Liver, Spleen

  4. Radiation response of mouse lymphoid and myeloid cell lines. Pt. 1

    International Nuclear Information System (INIS)

    Radford, I.R.

    1994-01-01

    The sensitivity of 10 mouse lymphoid or myeloid cell lines to γ-ray- and DNA-associated 125 I-decay-induced clonogenic cell killing have been compared with their rate of loss of viability (membrane integrity) and with their putative cell type of origin. The increased sensitivity of haematopoietic cell lines to killing by DNA dsb may be related to their mode of death (apoptosis versus necrosis). Mode of cell death may thus be an important factor in determining the 'inherent radiosensitivity' of normal cells/tissues. Haematopoietic cell lines that undergo rapid interphase apoptotic death showed extreme sensitivity to DNA dsb. (author)

  5. Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles.

    Science.gov (United States)

    Choi, Yohan; Wilson, Kalin; Hannon, Patrick R; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E; Jo, Misung

    2017-06-01

    In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients. The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured. PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes. This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells. Copyright © 2017 Endocrine Society

  6. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue.

    Science.gov (United States)

    Martinet, Kim Zita; Bloquet, Stéphane; Bourgeois, Christine

    2014-01-01

    CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer's patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary

  7. Androgen receptor in early apoptotic follicles in the porcine ovary at pregnancy.

    Directory of Open Access Journals (Sweden)

    Zbigniew Tabarowski

    2006-09-01

    Full Text Available Localization of androgen receptor (AR was investigated in ovarian follicles developing and undergoing atresia during pregnancy in the pig. Immunohistochemical staining was conducted on ovarian antral follicles isolated on different days of gestation: 10, 18, 32, 50, 70, and 90. Paraffin sections were also subjected to in situ DNA labeling. TUNEL staining revealed the presence of positive follicles on all days of pregnancy but the amount of atretic follicles increased with time. However, even on day 90 of gestation many follicles were normal, with no signs of atresia. In atretic follicles, apoptotic cells were localized predominantly in the granulosa while theca was much less affected. Atretic follicles with many apoptotic cells were negative for AR. Nuclear immunostaining for AR was positive in follicles with limited amount of apoptotic cells. The same relationship was observed in ovarian follicles isolated at various days of pregnancy.

  8. Overriding follicle selection in controlled ovarian stimulation protocols: Quality vs quantity

    Directory of Open Access Journals (Sweden)

    Zelinski-Wooten Mary B

    2004-06-01

    Full Text Available Abstract Selection of the species-specific number of follicles that will develop and ovulate during the ovarian cycle can be overridden by increasing the levels of pituitary gonadotropin hormones, FSH and LH. During controlled ovarian stimulation (COS in nonhuman primates for assisted reproductive technology (ART protocols, the method of choice (but not the only method has been the administration of exogenous gonadotropins, either of nonprimate or primate origin. Due to species-specificity of the primate LH (but not FSH receptor, COS with nonprimate (e.g., PMSG hormones can be attributed to their FSH activity. Elevated levels of FSH alone will produce large antral follicles containing oocytes capable of fertilization in vitro (IVF. However, there is evidence that LH, probably in lesser amounts, increases the rate of follicular development, reduces heterogeneity of the antral follicle pool, and improves the viability and rate of pre-implantation development of IVF-produced embryos. Since an endogenous LH surge typically does not occur during COS cycles (especially when a GnRH antagonist is added, a large dose of an LH-like hormone (i.e., hCG may be given to reinitiate meiosis and produce fertilizable oocytes. Alternate approaches using exogenous LH (or FSH, or GnRH agonist to induce an endogenous LH surge, have received lesser attention. Current protocols will routinely yield dozens of large follicles with fertilizable eggs. However, limitations include non/poor-responding animals, heterogeneity of follicles (and presumably oocytes and subsequent short luteal phases (limiting embryo transfer in COS cycles. However, the most serious limitation to further improvements and expanded use of COS protocols for ART is the lack of availability of nonhuman primate gonadotropins. Human, and even more so, nonprimate gonadotropins are antigenic in monkeys, which limits the number of COS cycles to as few as 1 (PMSG or 3 (recombinant hCG protocols in macaques

  9. Enhancing hair follicle regeneration by nonablative fractional laser: Assessment of irradiation parameters and tissue response.

    Science.gov (United States)

    Wu, Yueh-Feng; Wang, Shiou-Han; Wu, Pei-Shan; Fan, Sabrina Mai-Yi; Chiu, Hsien-Yi; Tsai, Tsung-Hua; Lin, Sung-Jan

    2015-04-01

    Identification of methods to enhance anagen entry can be helpful for alopecia. Recently, nonablative laser has been proposed as a potential treatment for alopecia. However, how the laser parameters affect stem cell activity, hair cycles and the associated side effects have not been well characterized. Here we examine the effects of irradiation parameters of 1,550-nm fractional laser on hair cycles. The dorsal skin of eight-week-old female C57BL/6 mice with hair follicles in synchronized telogen was shaved and irradiated with a 1,550-nm fractional erbium-glass laser (Fraxel RE:STORE (SR1500) Laser System, Solta Medical, U.S.A.) with varied beam energies (5-35 mJ) and beam densities (500-3500 microthermal zones/cm(2) ). The cutaneous changes were evaluated both grossly and histologically. Hair follicle stem cell activity was detected by BrdU incorporation and changes in gene expression were quantified by real-time PCR. Direct thermal injury to hair follicles could be observed early after irradiation, especially at higher beam energy. Anagen induction in the irradiated skin showed an all-or-non change. Anagen induction and ulcer formation were affected by the combination of beam energy and density. The lowest beam energy of 5 mJ failed to promote anagen entry at all beam densities tested. As beam energy increased from 10 mJ to 35 mJ, we found a decreasing trend of beam density that could induce anagen entry within 7-9 days with activation of hair follicle stem cells. Beam density above the pro-regeneration density could lead to ulcers and scarring followed by anagen entry in adjacent skin. Analysis of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, revealed that transient moderate inflammation was associated with anagen induction and intense prolonged inflammation preceded ulcer formation. To avoid side effects of hair follicle injury and scarring, appropriate combination of beam energy and density is required. Parameters outside the therapeutic

  10. Computer-generated ovaries to assist follicle counting experiments.

    Directory of Open Access Journals (Sweden)

    Angelos Skodras

    Full Text Available Precise estimation of the number of follicles in ovaries is of key importance in the field of reproductive biology, both from a developmental point of view, where follicle numbers are determined at specific time points, as well as from a therapeutic perspective, determining the adverse effects of environmental toxins and cancer chemotherapeutics on the reproductive system. The two main factors affecting follicle number estimates are the sampling method and the variation in follicle numbers within animals of the same strain, due to biological variability. This study aims at assessing the effect of these two factors, when estimating ovarian follicle numbers of neonatal mice. We developed computer algorithms, which generate models of neonatal mouse ovaries (simulated ovaries, with characteristics derived from experimental measurements already available in the published literature. The simulated ovaries are used to reproduce in-silico counting experiments based on unbiased stereological techniques; the proposed approach provides the necessary number of ovaries and sampling frequency to be used in the experiments given a specific biological variability and a desirable degree of accuracy. The simulated ovary is a novel, versatile tool which can be used in the planning phase of experiments to estimate the expected number of animals and workload, ensuring appropriate statistical power of the resulting measurements. Moreover, the idea of the simulated ovary can be applied to other organs made up of large numbers of individual functional units.

  11. Protein biosynthesis in cultured human hair follicle cells.

    Science.gov (United States)

    Weterings, P J; Vermorken, A J; Bloemendal, H

    1980-10-31

    A new technique has been used for culturing human keratinocytes. The cells grow on the basement membrane-like capsules of bovine lenses. Lens cells were removed from the capsules by rigid trypsinization. In order to exclude any contamination with remaining living cells the isolated capsules were irradiated with X-rays at a dose of 10,000 rad. In this way human epithelial cells can be brought in culture from individual hair follicles. Since feeder cells are not used in this culture technique, the biosynthesis of keratinocyte proteins can be studied in these cultures. The newly synthesized proteins can be separated into a water-soluble, a urea-soluble, and a urea-insoluble fraction. Product analysis has been performed on the first two fractions revealing protein patterns identical to those of intact hair follicles. Product analysis of the urea-soluble fractions of microdissected hair follicles shows that the protein pattern of the cultured keratinocytes resembles the protein pattern of the hair follicle sheath. Studies on the metabolism of benzo(a)pyrene revealed that the enzyme aryl hydrocarbon hydroxylase (AHH) is present in cultured hair follicle cells. A possible use of our culture system for eventual detection of inherited predisposition for smoking-dependent lung cancer is discussed.

  12. ILK modulates epithelial polarity and matrix formation in hair follicles.

    Science.gov (United States)

    Rudkouskaya, Alena; Welch, Ian; Dagnino, Lina

    2014-03-01

    Hair follicle morphogenesis requires coordination of multiple signals and communication between its epithelial and mesenchymal constituents. Cell adhesion protein platforms, which include integrins and integrin-linked kinase (ILK), are critical for hair follicle formation. However, their precise contribution to this process is poorly understood. We show that in the absence of ILK, the hair follicle matrix lineage fails to develop, likely due to abnormalities in development of apical-basal cell polarity, as well as in laminin-511 and basement membrane assembly at the tip of the hair bud. These defects also result in impaired specification of hair matrix and absence of precortex and inner sheath root cell lineages. The molecular pathways affected in ILK-deficient follicles are similar to those in the absence of epidermal integrin β1 and include Wnt, but not sonic hedgehog, signaling. ILK-deficient hair buds also show abnormalities in the dermal papilla. Addition of exogenous laminin-511 restores morphological and molecular markers associated with hair matrix formation, indicating that ILK regulates hair bud cell polarity and functions upstream from laminin-511 assembly to regulate the developmental progression of hair follicles beyond the germ stage.

  13. Close Encounters of Lymphoid Cells and Bacteria

    Science.gov (United States)

    Cruz-Adalia, Aranzazu; Veiga, Esteban

    2016-01-01

    During infections, the first reaction of the host against microbial pathogens is carried out by innate immune cells, which recognize conserved structures on pathogens, called pathogen-associated molecular patterns. Afterward, some of these innate cells can phagocytose and destroy the pathogens, secreting cytokines that would modulate the immune response to the challenge. This rapid response is normally followed by the adaptive immunity, more specific and essential for a complete pathogen clearance in many cases. Some innate immune cells, usually named antigen-presenting cells, such as macrophages or dendritic cells, are able to process internalized invaders and present their antigens to lymphocytes, triggering the adaptive immune response. Nevertheless, the traditional boundary of separated roles between innate and adaptive immunity has been blurred by several studies, showing that very specialized populations of lymphocytes (cells of the adaptive immunity) behave similarly to cells of the innate immunity. These “innate-like” lymphocytes include γδ T cells, invariant NKT cells, B-1 cells, mucosal-associated invariant T cells, marginal zone B cells, and innate response activator cells, and together with the newly described innate lymphoid cells are able to rapidly respond to bacterial infections. Strikingly, our recent data suggest that conventional CD4+ T cells, the paradigm of cells of the adaptive immunity, also present innate-like behavior, capturing bacteria in a process called transinfection. Transinfected CD4+ T cells digest internalized bacteria like professional phagocytes and secrete large amounts of proinflammatory cytokines, protecting for further bacterial challenges. In the present review, we will focus on the data showing such innate-like behavior of lymphocytes following bacteria encounter. PMID:27774092

  14. Unscheduled DNA synthesis in human hair follicles after in vitro exposure to 11 chemicals: comparison with unscheduled DNA synthesis in rat hepatocytes.

    Science.gov (United States)

    van Erp, Y H; Koopmans, M J; Heirbaut, P R; van der Hoeven, J C; Weterings, P J

    1992-06-01

    A new method is described to investigate unscheduled DNA synthesis (UDS) in human tissue after exposure in vitro: the human hair follicle. A histological technique was applied to assess cytotoxicity and UDS in the same hair follicle cells. UDS induction was examined for 11 chemicals and the results were compared with literature findings for UDS in rat hepatocytes. Most chemicals inducing UDS in rat hepatocytes raised DNA repair at comparable concentrations in the hair follicle. However, 1 of 9 chemicals that gave a positive response in the rat hepatocyte UDS test, 2-acetylaminofluorene, failed to induce DNA repair in the hair follicle. Metabolizing potential of hair follicle cells was shown in experiments with indirectly acting compounds, i.e., benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene and dimethylnitrosamine. The results support the conclusion that the test in its present state is valuable as a screening assay for the detection of unscheduled DNA synthesis. Moreover, the use of human tissues may result in a better extrapolation to man.

  15. Stem cell dynamics in the hair follicle niche

    Science.gov (United States)

    Rompolas, Panteleimon; Greco, Valentina

    2014-01-01

    Hair follicles are skin appendages of the mammalian skin that have the ability to periodically and stereotypically regenerate in order to continuously produce new hair over our lifetime. The ability of the hair follicle to regenerate is due to the presence of stem cells that along with other cell populations and non-cellular components, including molecular signals and extracellular material, make up a niche microenvironment. Mounting evidence suggests that the niche is critical for regulating stem cell behavior and thus the process of regeneration. Here we review the literature concerning past and current studies that have utilized mouse genetic models, combined with other approaches to dissect the molecular and cellular composition of the hair follicle niche. We also discuss our current understanding of how stem cells operate within the niche during the process of tissue regeneration and the factors that regulate their behavior. PMID:24361866

  16. Acute doxorubicin insult in the mouse ovary is cell- and follicle-type dependent.

    Directory of Open Access Journals (Sweden)

    Elon C Roti Roti

    Full Text Available Primary ovarian insufficiency (POI is one of the many unintended consequences of chemotherapy faced by the growing number of female cancer survivors. While ovarian repercussions of chemotherapy have long been recognized, the acute insult phase and primary sites of damage are not well-studied, hampering efforts to design effective intervention therapies to protect the ovary. Utilizing doxorubicin (DXR as a model chemotherapy agent, we defined the acute timeline for drug accumulation, induced DNA damage, and subsequent cellular and follicular demise in the mouse ovary. DXR accumulated first in the core ovarian stroma cells, then redistributed outwards into the cortex and follicles in a time-dependent manner, without further increase in total ovarian drug levels after four hours post-injection. Consistent with early drug accumulation and intimate interactions with the blood supply, stroma cell-enriched populations exhibited an earlier DNA damage response (measurable at 2 hours than granulosa cells (measurable at 4 hours, as quantified by the comet assay. Granulosa cell-enriched populations were more sensitive however, responding with greater levels of DNA damage. The oocyte DNA damage response was delayed, and not measurable above background until 10-12 hours post-DXR injection. By 8 hours post-DXR injection and prior to the oocyte DNA damage response, the number of primary, secondary, and antral follicles exhibiting TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive granulosa cells plateaued, indicating late-stage apoptosis and suggesting damage to the oocytes is subsequent to somatic cell failure. Primordial follicles accumulate significant DXR by 4 hours post-injection, but do not exhibit TUNEL-positive granulosa cells until 48 hours post-injection, indicating delayed demise. Taken together, the data suggest effective intervention therapies designed to protect the ovary from chemotherapy accumulation and induced insult

  17. Acute Doxorubicin Insult in the Mouse Ovary Is Cell- and Follicle-Type Dependent

    Science.gov (United States)

    Roti Roti, Elon C.; Leisman, Scott K.; Abbott, David H.; Salih, Sana M.

    2012-01-01

    Primary ovarian insufficiency (POI) is one of the many unintended consequences of chemotherapy faced by the growing number of female cancer survivors. While ovarian repercussions of chemotherapy have long been recognized, the acute insult phase and primary sites of damage are not well-studied, hampering efforts to design effective intervention therapies to protect the ovary. Utilizing doxorubicin (DXR) as a model chemotherapy agent, we defined the acute timeline for drug accumulation, induced DNA damage, and subsequent cellular and follicular demise in the mouse ovary. DXR accumulated first in the core ovarian stroma cells, then redistributed outwards into the cortex and follicles in a time-dependent manner, without further increase in total ovarian drug levels after four hours post-injection. Consistent with early drug accumulation and intimate interactions with the blood supply, stroma cell-enriched populations exhibited an earlier DNA damage response (measurable at 2 hours) than granulosa cells (measurable at 4 hours), as quantified by the comet assay. Granulosa cell-enriched populations were more sensitive however, responding with greater levels of DNA damage. The oocyte DNA damage response was delayed, and not measurable above background until 10–12 hours post-DXR injection. By 8 hours post-DXR injection and prior to the oocyte DNA damage response, the number of primary, secondary, and antral follicles exhibiting TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive granulosa cells plateaued, indicating late-stage apoptosis and suggesting damage to the oocytes is subsequent to somatic cell failure. Primordial follicles accumulate significant DXR by 4 hours post-injection, but do not exhibit TUNEL-positive granulosa cells until 48 hours post-injection, indicating delayed demise. Taken together, the data suggest effective intervention therapies designed to protect the ovary from chemotherapy accumulation and induced insult in the ovary

  18. Activation of dormant ovarian follicles to generate mature eggs.

    Science.gov (United States)

    Li, Jing; Kawamura, Kazuhiro; Cheng, Yuan; Liu, Shuang; Klein, Cynthia; Liu, Shu; Duan, En-Kui; Hsueh, Aaron J W

    2010-06-01

    Although multiple follicles are present in mammalian ovaries, most of them remain dormant for years or decades. During reproductive life, some follicles are activated for development. Genetically modified mouse models with oocyte-specific deletion of genes in the PTEN-PI3K-Akt-Foxo3 pathway exhibited premature activation of all dormant follicles. Using an inhibitor of the Phosphatase with TENsin homology deleted in chromosome 10 (PTEN) phosphatase and a PI3K activating peptide, we found that short-term treatment of neonatal mouse ovaries increased nuclear exclusion of Foxo3 in primordial oocytes. After transplantation under kidney capsules of ovariectomized hosts, treated follicles developed to the preovulatory stage with mature eggs displaying normal epigenetic changes of imprinted genes. After in vitro fertilization and embryo transfer, healthy progeny with proven fertility were delivered. Human ovarian cortical fragments from cancer patients were also treated with the PTEN inhibitor. After xeno-transplantation to immune-deficient mice for 6 months, primordial follicles developed to the preovulatory stage with oocytes capable of undergoing nuclear maturation. Major differences between male and female mammals are unlimited number of sperm and paucity of mature oocytes. Thus, short-term in vitro activation of dormant ovarian follicles after stimulation of the PI3K-Akt pathway allows the generation of a large supply of mature female germ cells for future treatment of infertile women with a diminishing ovarian reserve and for cancer patients with cryo-preserved ovaries. Generation of a large number of human oocytes also facilitates future derivation of embryonic stem cells for regenerative medicine.

  19. Atresia of large ovarian follicles of the rat

    Directory of Open Access Journals (Sweden)

    Maria Słomczyn´ ska

    2011-08-01

    Full Text Available In the rat, at the beginning of pregnancy a cohort of antral follicles develops until the preovulatory stage. However, these follicles, differentiating in the hyperprolactinemic milieu, produce only small amount of estradiol, do not ovulate and undergo rapid degeneration. They constitute an interesting physiological model of atresia. In the present study, we analysed the development and subsequent degeneration of such follicles. The study was performed on Wistar female rats killed in succession between days 1-9 of pregnancy. Excised ovaries were submitted to a routine histological procedure. Paraffin sections were subjected to hematoxylin and eosin staining or in situ DNA labelling. Histological and TUNEL staining revealed that the investigated group of follicles grew slower than that on the corresponding days of the estrous cycle and reached a preovulatory size and morphological appearance on day 5 of pregnancy. They did not ovulate and between days 6 and 9 of pregnancy an increasing number of apoptotic cells appeared within these follicles. They were localized predominantly in the antral granulosa layer, especially near the cumulus oophorus complex (COC and in the region linking the COC with the follicular wall. The COC and the theca layer were much less affected. In late stages of atresia, also cumulus cells became apoptotic but degenerating oocytes did not exhibit positive TUNEL staining. Only limited number of the theca cells have undergone apoptosis and generally they were not hypertrophied. Our findings indicate that much smaller than normal amount of intrafollicular estradiol was sufficient to support a normal, according to the morphological criteria, although slower development of antral follicles to the late preovulatory stage.

  20. [Rectal tonsil or lymphoid follicular hyperplasia of the rectum].

    Science.gov (United States)

    Trillo Fandiño, L; Arias González, M; Iglesias Castañón, A; Fernández Eire, M P

    2014-01-01

    The rectal tonsil is a reactive proliferation of lymphoid tissue located in the rectum. The morphology of the lymphoid proliferation of the colon is usually polypoid or, less commonly, nodular. Only in exceptional cases does lymphoid proliferation of the colon present as a mass in the rectum (rectal tonsil), although this is the most common presentation in middle-aged patients. It is important to be familiar with the rectal tonsil because in cases of exuberant growth it can be difficult to distinguish it from other types of masses. We present the case of rectal tonsil in a four-year-old girl. We describe the magnetic resonance imaging findings and review the literature. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  1. Radiation response of mouse lymphoid and myeloid cell lines. Pt. 3

    International Nuclear Information System (INIS)

    Radford, I.R.; Murphy, T.K.

    1994-01-01

    The authors have examined the timing of γ-irradiation-induced death in relation to cell cycle progression using a panel of mouse lymphoid or myeloid cell lines. Death was found to occur immediately after irradiation ('rapid interphase' death), or after arrest in G 2 phase ('delayed interphase' death), or following one or more mitoses ('mitotic/delayed mitotic' death). In part II of this series of papers the authors demonstrated the occurrence of radiation-induced apoptosis in all these cell lines. Several of the cell lines showed different timing of death dependent upon the radiation dose used. These differences in the timing of radiation-induced death are shown to be useful indicators of the relative radiosensitivity of haematopoietic cell lines. (author)

  2. Apparent clusters of childhood lymphoid malignancy in Northern England

    International Nuclear Information System (INIS)

    Craft, A.W.; Openshaw, S.; Birch, J.

    1984-01-01

    The authors have reanalysed their previous data on the incidence of childhood malignancy in the North of England by very small geographical areas. Seascale, which ranks first by Poisson probability for all lymphoid malignancies is the village closest to the Sellafield plant. However, it is not unique in the region; nor are wards of apparent excess confined to coastal areas of Cumbria. The highest rate of lymphoid malignancies is in Whittingham, a village in north Northumberland. For other varieties of childhood cancer, there is a similar spread of 'Highly ranked', but different, wards throughout the region. (U.K.)

  3. Mature lymphoid malignancies: origin, stem cells, and chronicity

    DEFF Research Database (Denmark)

    Husby, Simon; Grønbæk, Kirsten

    2017-01-01

    after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell...... population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source...

  4. Introduction of transplantation tolerance after total lymphoid irradiation: cellular mechanisms

    International Nuclear Information System (INIS)

    Strober, S.; King, D.P.; Gottlieb, M.; Hoppe, R.T.; Kaplan, H.S.

    1981-01-01

    High-dose fractionated total lymphoid irradiation (TLI) is a safe, routine regimen used to treat patients with lymphoid malignancies. Although few side effects are associated with the regimen, a profound suppression of cell-mediated immunity is observed for several years after therapy, as judged by both in vivo and in vitro assays. A profound immunosuppression has also been observed in mice and rats given TLI. Recently, we have achieved similar results using TLI in nonmatched bone marrow transplantation in outbred dogs. The experimental work in animals and underlying cellular mechanisms are reviewed here

  5. Bronchus-associated lymphoid tissue (BALT and survival in a vaccine mouse model of tularemia.

    Directory of Open Access Journals (Sweden)

    Damiana Chiavolini

    2010-06-01

    Full Text Available Francisella tularensis causes severe pulmonary disease, and nasal vaccination could be the ideal measure to effectively prevent it. Nevertheless, the efficacy of this type of vaccine is influenced by the lack of an effective mucosal adjuvant.Mice were immunized via the nasal route with lipopolysaccharide isolated from F. tularensis and neisserial recombinant PorB as an adjuvant candidate. Then, mice were challenged via the same route with the F. tularensis attenuated live vaccine strain (LVS. Mouse survival and analysis of a number of immune parameters were conducted following intranasal challenge. Vaccination induced a systemic antibody response and 70% of mice were protected from challenge as showed by their improved survival and weight regain. Lungs from mice recovering from infection presented prominent lymphoid aggregates in peribronchial and perivascular areas, consistent with the location of bronchus-associated lymphoid tissue (BALT. BALT areas contained proliferating B and T cells, germinal centers, T cell infiltrates, dendritic cells (DCs. We also observed local production of antibody generating cells and homeostatic chemokines in BALT areas.These data indicate that PorB might be an optimal adjuvant candidate for improving the protective effect of F. tularensis antigens. The presence of BALT induced after intranasal challenge in vaccinated mice might play a role in regulation of local immunity and long-term protection, but more work is needed to elucidate mechanisms that lead to its formation.

  6. File list: InP.Bld.50.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Lymphoid_cells mm9 Input control Blood Lymphoid cells SRX021894,SR...X971601 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.50.AllAg.Lymphoid_cells.bed ...

  7. File list: ALL.Bld.20.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Lymphoid_cells mm9 All antigens Blood Lymphoid cells SRX658437,SRX...658389,SRX021894,SRX971603,SRX658419,SRX971601,SRX971602,SRX658405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.20.AllAg.Lymphoid_cells.bed ...

  8. File list: ALL.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Lymphoid_cells mm9 All antigens Blood Lymphoid cells SRX658419,SRX...658405,SRX658389,SRX658437,SRX971601,SRX971603,SRX021894,SRX971602 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.Lymphoid_cells.bed ...

  9. File list: InP.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Lymphoid_cells mm9 Input control Blood Lymphoid cells SRX971601,SR...X021894 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Lymphoid_cells.bed ...

  10. File list: ALL.Bld.50.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Lymphoid_cells mm9 All antigens Blood Lymphoid cells SRX658389,SRX...021894,SRX658437,SRX971603,SRX971601,SRX971602,SRX658419,SRX658405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.Lymphoid_cells.bed ...

  11. File list: InP.Bld.20.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.Lymphoid_cells mm9 Input control Blood Lymphoid cells SRX021894,SR...X971601 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.20.AllAg.Lymphoid_cells.bed ...

  12. File list: His.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Lymphoid_cells mm9 Histone Blood Lymphoid cells SRX658419,SRX65840...5,SRX658389,SRX658437,SRX971603,SRX971602 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.Lymphoid_cells.bed ...

  13. The effects of prolonged oral administration of gold nanoparticles on the morphology of hematopoietic and lymphoid organs

    Science.gov (United States)

    Bucharskaya, Alla B.; Pakhomy, Svetlana S.; Zlobina, Olga V.; Maslyakova, Galina N.; Navolokin, Nikita A.; Matveeva, Olga V.; Khlebtsov, Boris N.; Bogatyrev, Vladimir A.; Khlebtsov, Nikolai G.; Tuchin, Valery V.

    2017-02-01

    Currently, the usage of gold nanoparticles as photosensitizers and immunomodulators for plasmonic photothermal therapy has attracted a great attention of researches and end-users. In our work, the influence of prolonged peroral administration of gold nanoparticles (GNPs) with different sizes on the morphological changes of hematopoietic and lymphoid organs was investigated. The 24 white outbred male rats weighing 180-220 g were randomly divided into groups and administered orally for 30 days the suspension of gold nanospheres with diameters of 2, 15 and 50 nm at a dosage of 190 μg/kg of animal body weight. To prevent GNPs aggregation in a tissue and enhance biocompatibility, they were functionalized with thiolated polyethylene glycol. The withdrawal of the animals from the experiment and sampling of spleen, lymph nodes and bone marrow tissues for morphological study were performed a day after the last administration. In the spleen the boundary between the red and white pulp was not clearly differ in all experimental groups, lymphoid follicles were significantly increased in size, containing bright germinative centers represented by large blast cells. The stimulation of lymphocyte and myelocytic series of hematopoiesis was recorded at morphological study of the bone marrow. The number of immunoblasts and large lymphocytes was increased in all structural zones of lymph nodes. The more pronounced changes were found in the group with administration of 15 nm nanoparticles. Thus, the morphological changes of cellular components of hematopoietic organs have size-dependent character and indicate the activation of the migration, proliferation and differentiation of immune cells after prolonged oral administration of GNPs.

  14. The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions

    Directory of Open Access Journals (Sweden)

    Thibaut Perchet

    2018-06-01

    Full Text Available The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC. We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade. Indeed, type 1 ILC comprises conventional NK (cNK cells and type 1 helper innate lymphoid cells (ILC1 that share Notch-related functional characteristics such as the IFNg secretion downstream of T-bet expression. cNK cells have strong antitumor properties. However, data are controversial concerning ILC1 functions during carcinogenesis with models showing antitumoral capacities and others reporting ILC1 inability to control tumor growth. Using various mouse models of Notch signaling pathway depletion, we analyze the effects of its absence on type 1 ILC differentiation and cytotoxic functions. We also provide clues into its role in the maintenance of immune homeostasis in tissues. We show that modulating the Notch pathway is not only acting on tumor-specific T cell activity but also on ILC immune subset functions. Hence, our study uncovers the intrinsic Notch signaling pathway in ILC1/cNK populations and their response in case of abnormal Notch ligand expression. This study help evaluating the possible side effects mediated by immune cells different from T cells, in case of multivalent forms of the Notch receptor ligand delta 1 treatments. In definitive, it should help determining the best novel combination of therapeutic strategies in case of solid tumors.

  15. Innate Lymphoid Cells Mediate Pulmonary Eosinophilic Inflammation, Airway Mucous Cell Metaplasia, and Type 2 Immunity in Mice Exposed to Ozone.

    Science.gov (United States)

    Kumagai, Kazuyoshi; Lewandowski, Ryan P; Jackson-Humbles, Daven N; Buglak, Nicholas; Li, Ning; White, Kaylin; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2017-08-01

    Exposure to elevated levels of ambient ozone in photochemical smog is associated with eosinophilic airway inflammation and nonatopic asthma in children. In the present study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced nonatopic asthma by using lymphoid cell-sufficient C57BL/6 mice, ILC-sufficient Rag2 -/- mice (devoid of T and B cells), and ILC-deficient Rag2 -/- Il2rg -/- mice (depleted of all lymphoid cells including ILCs). Mice were exposed to 0 or 0.8 parts per million ozone for 1 day or 9 consecutive weekdays (4 hr/day). A single exposure to ozone caused neutrophilic inflammation, airway epithelial injury, and reparative DNA synthesis in all strains of mice, irrespective of the presence or absence of ILCs. In contrast, 9-day exposures induced eosinophilic inflammation and mucous cell metaplasia only in the lungs of ILC-sufficient mice. Repeated ozone exposures also elicited increased messenger RNA expression of transcripts associated with type 2 immunity and airway mucus production in ILC-sufficient mice. ILC-deficient mice repeatedly exposed to ozone had no pulmonary pathology or increased gene expression related to type 2 immunity. These results suggest a new paradigm for the biologic mechanisms underlying the development of a phenotype of childhood nonatopic asthma that has been linked to ambient ozone exposures.

  16. Interleukin-7 Availability Is Maintained by a Hematopoietic Cytokine Sink Comprising Innate Lymphoid Cells and T Cells.

    Science.gov (United States)

    Martin, Christopher E; Spasova, Darina S; Frimpong-Boateng, Kwesi; Kim, Hee-Ok; Lee, Minji; Kim, Kwang Soon; Surh, Charles D

    2017-07-18

    Interleukin-7 (IL-7) availability determines the size and proliferative state of the resting T cell pool. However, the mechanisms that regulate steady-state IL-7 amounts are unclear. Using experimental lymphopenic mouse models and IL-7-induced homeostatic proliferation to measure IL-7 availability in vivo, we found that radioresistant cells were the source of IL-7 for both CD4 + and CD8 + T cells. Hematopoietic lineage cells, although irrelevant as a source of IL-7, were primarily responsible for limiting IL-7 availability via their expression of IL-7R. Unexpectedly, innate lymphoid cells were found to have a potent influence on IL-7 amounts in the primary and secondary lymphoid tissues. These results demonstrate that IL-7 homeostasis is achieved through consumption by multiple subsets of innate and adaptive immune cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. In vitro effects of diethylstilbestrol, genistein, 4-tert-butylphenol, and 4-tert-octylphenol on steroidogenic activity of isolated immature rat ovarian follicles

    International Nuclear Information System (INIS)

    Myllymaeki, Sari; Haavisto, Tapio; Vainio, Minna; Toppari, Jorma; Paranko, Jorma

    2005-01-01

    Isolated rat ovarian follicles grow and produce steroid hormones in vitro and so provide a good model for studying the effects of hormonally active compounds on follicular steroidogenesis. We have evaluated the effects of diethylstilbestrol (DES), genistein (GEN) and two alkylphenols, 4-tert-butylphenol (BP) and 4-tert-octylphenol (OP) on the growth, survival, and steroid hormone and cAMP production by isolated 14-day-old rat (Sprague-Dawley) ovarian follicles. During a 5-day culture, FSH was obligatory for follicle growth and increased estradiol and testosterone secretion in a dose-dependent manner. DES (10 -6 M) caused the strongest decline in estradiol and testosterone levels but did not have detectable effects on either cAMP production or aromatase enzyme activity. GEN caused a prominent decrease in cAMP and testosterone levels without significant changes in secreted estradiol. The latter, apparently, was due to a dose-dependent stimulation of aromatase enzyme activity in the presence of genistein. Both BP and OP decreased estradiol and testosterone secretion in a dose-dependent manner while no effect on aromatase activity was observed. OP, unlike BP, decreased forskolin-induced cAMP levels. Xenoestrogens at the used concentrations did not interfere with the growth and survival of the follicles. The results indicate that isolated ovarian follicles representing intact morphological and functional units offer a sensitive model system for elucidating the female-specific reproductive effects of environmental chemicals

  18. Human hair follicle benzo(a)pyrene and benzo(a)pyrene 7, 8-diol metabolism: effect of exposure to a coal tar-containing shampoo

    Energy Technology Data Exchange (ETDEWEB)

    Merk, H.F.; Mukhtar, H.; Kaufmann, I.; Das, M.; Bickers, D.R.

    1987-01-01

    Hair follicles are a readily available source of human epithelial tissue and offer an excellent system with which to study carcinogen metabolism in human populations. In this study hair follicles were employed to measure the metabolism of benzo(a)pyrene (BP), benzo(a)pyrene - 7,8-diol (BP 7,8-diol) and the enzyme mediated binding of /sup 3/H-BP to DNA. The effect of human exposure to a crude coal tar (CCT) - containing shampoo, a preparation rich in polycyclic aromatic hydrocarbons (PAHs on these parameters was also evaluated. It was found that aryl hydrocarbon hydroxylase (AHH) activity increased after use of the shampoo and enhancement of enzyme-mediated binding of BP to DNA was detected in most subjects. Hair follicles were shown to convert BP to several metabolic species and BP, 7,8-diol was also metabolised. Clotrimazole, a known inhibitor of the metabolism of BP was found to inhibit AHH and the metabolism of BP and BP 7,8-diol in human hair follicles, as were other imidazole compounds. The studies show that hair follicles represent an accessible tissue suitable for assessing the extent of PAH carcinogen metabolism in human subjects. Furthermore enzyme activity critical to cancer induction by PAHs was shown to be inducible following the use of a CCT-containing shampoo. Imidazole compounds were shown to be possible effective anti-carcinogens in human populations. 29 refs.

  19. Effects of Moringa oleifera Lam. aqueous leaf extracts on follicle ...

    African Journals Online (AJOL)

    The study evaluated the effect of Moringa oleifera aqueous leaf extracts on follicle stimulating hormone and serum cholesterol in Wistar rats. Thirty six (36) mature Wistar rats (20 male and 16 female rats) were used. The male rats were grouped into four groups with five animals each, while the female animals were grouped ...

  20. Comparative phenotypic characterization of keratinocytes originating from hair follicles

    Czech Academy of Sciences Publication Activity Database

    Klíma, Jiří; Smetana Jr., K.; Motlík, Jan; Plzáková, Z.; Liu, F. T.; Štork, J.; Kaltner, H.; Chovanec, M.; Dvořánková, B.; André, S.; Gabius, H. J.

    2005-01-01

    Roč. 36, - (2005), s. 89-96 R&D Projects: GA MŠk(CZ) LN00A065; GA AV ČR IBS4050005; GA ČR(CZ) GA304/04/0171 Institutional research plan: CEZ:AV0Z50450515 Keywords : hair follicles Subject RIV: EB - Genetics ; Molecular Biology

  1. Female reproductive anatonlY and developnlent of ovarian follicles ...

    African Journals Online (AJOL)

    occurs before hibernation (Vander Merwe 1979), the cells of the cumulus oophorus do not show any marked hyper- trophy. Miniopterusjraterculus, the species under study, is a hibernating vespertilionid, and as in M. schreibersi ovula- tion occurs before hibernation. Although a large number of follicles begin development.

  2. Radioimmunoassay of follicle stimulating hornone in human plasma

    International Nuclear Information System (INIS)

    Akande, E.O.

    1976-01-01

    A radioimmunoassay method for Follicle Stimulating Hormone (fsh) in human plasma is described. The method proved to be reliable in determining fsh levels in normally menstruating women as well as women in varying clinical states. The patterns and levels of fsh obtained from 16 menstrual cycles in 12 normally menstruating women showed agreement with previous results of Franchimont, Faiman and Ryan, etc

  3. GnRH injection before artificial insemination (AI) alters follicle ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... releasing hormone (GnRH) injection on day 6 of the estrous cycle. The estrous cycles ... follicle at the time of GnRH injection (Silcox et al., 1993;. Twagiramungu .... Waves and their Effect on pregnancy rate in the Cow. Reprod.

  4. Effect of PCB 126 on aryl hydrocarbon receptor 1 (AHR1) and AHR1 nuclear translocator 1 (ARNT1) mRNA expression and CYP1 monooxygenase activity in chicken (Gallus domesticus) ovarian follicles.

    Science.gov (United States)

    Wójcik, Dagmara; Antos, Piotr A; Katarzyńska, Dorota; Hrabia, Anna; Sechman, Andrzej

    2015-12-03

    The aim of the experiment was to study the in vitro effect of 3,3',4,4',5-pentachlorobiphenyl (PCB 126; a coplanar PCB congener) on aryl hydrocarbon receptor (AHR1) and AHR1 nuclear translocator (ARNT1) mRNA expression and the activity of CYP1 family monooxygenases in chicken ovarian follicles. White (1-4 mm) and yellowish (4-8 mm) prehierarchical follicles as well as fragments of the theca and granulosa layers of the 3 largest preovulatory follicles (F3-F1) were incubated in a medium supplemented with 0 (control group), 1, 10 or 100 nM PCB 126. The incubation was carried out for 6 h or 24 h for determination of mRNA expression of AHR1 and ARNT1 genes (real-time qPCR) and CYP1 monooxygenase activity (EROD and MROD fluorometric assays), respectively. It was found that chicken ovarian follicles express mRNA of AHR1 and ARNT1 genes. A modulatory effect of PCB 126 on AHR1 and ARNT1 expression depended not only on the biphenyl concentration but also on the follicular layer and the maturational state of the follicle. EROD and MROD activities appeared predominantly in the granulosa layer of the yellow preovulatory follicles. PCB 126 induced these activities in a dose-dependent manner in all ovarian follicles. The obtained results suggest that ovarian follicles, especially the granulosa layer, are involved in the detoxification process of PCBs in the laying hen. Taking this finding into consideration it can be suggested that the granulosa layer of the yellow hierarchical follicles plays a key role in the protective mechanism which reduces the amount of transferred dioxin-like compounds into the yolk of the oocyte. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. THE EXTENT OF CLONAL STRUCTURE IN DIFFERENT LYMPHOID ORGANS

    NARCIS (Netherlands)

    HERMANS, MHA; WUBBENA, A; KROESE, FGM; HUNT, SV; COWAN, R; OPSTELTEN, D

    1992-01-01

    To gain insight into the clonal organization of lymphoid organs, we studied the distribution in situ of donor-derived cells in near-physiological chimeras. We introduced RT7b fetal liver cells into nonirradiated congenic RT7a neonatal rats. The chimerism 6-20 wk after injection ranged from 0.3 to

  6. Innate lymphoid cells and parasites: Ancient foes with shared history.

    Science.gov (United States)

    Neill, D R; Fallon, P G

    2018-02-01

    This special issue of Parasite Immunology charts the rapid advances made in our understanding of the myriad interactions between innate lymphoid cells and parasites and how these interactions have shaped our evolutionary history. Here, we provide an overview of the issue and highlight key findings from studies in mice and man. © 2017 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

  7. Developmental acquisition of regulomes underlies innate lymphoid cell functionality

    Science.gov (United States)

    Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis, and they mirror adaptive CD4+ T helper (Th) cell subtypes in both usages of effector molecules and ·transcription factors. To better understand ILC subsets and their relationship with Th cells, we measur...

  8. Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.

    Science.gov (United States)

    Mortha, Arthur; Burrows, Kyle

    2018-01-01

    Innate lymphoid cells (ILCs) are an essential component of the innate immune system in vertebrates. They are developmentally rooted in the lymphoid lineage and can diverge into at least three transcriptionally distinct lineages. ILCs seed both lymphoid and non-lymphoid tissues and are locally self-maintained in tissue-resident pools. Tissue-resident ILCs execute important effector functions making them key regulator in tissue homeostasis, repair, remodeling, microbial defense, and anti-tumor immunity. Similar to T lymphocytes, ILCs possess only few sensory elements for the recognition of non-self and thus depend on extrinsic cellular sensory elements residing within the tissue. Myeloid cells, including mononuclear phagocytes (MNPs), are key sentinels of the tissue and are able to translate environmental cues into an effector profile that instructs lymphocyte responses. The adaptation of myeloid cells to the tissue state thus influences the effector program of ILCs and serves as an example of how environmental signals are integrated into the function of ILCs via a tissue-resident immune cell cross talks. This review summarizes our current knowledge on the role of myeloid cells in regulating ILC functions and discusses how feedback communication between ILCs and myeloid cells contribute to stabilize immune homeostasis in order to maintain the healthy state of an organ.

  9. Innate lymphoid cells--a proposal for uniform nomenclature

    NARCIS (Netherlands)

    Spits, Hergen; Artis, David; Colonna, Marco; Diefenbach, Andreas; Di Santo, James P.; Eberl, Gerard; Koyasu, Shigeo; Locksley, Richard M.; McKenzie, Andrew N. J.; Mebius, Reina E.; Powrie, Fiona; Vivier, Eric

    2013-01-01

    Innate lymphoid cells (ILCs) are a family of developmentally related cells that are involved in immunity and in tissue development and remodelling. Recent research has identified several distinct members of this family. Confusingly, many different names have been used to characterize these newly

  10. Innate lymphoid cells: the new kids on the block.

    Science.gov (United States)

    Withers, David R; Mackley, Emma C; Jones, Nick D

    2015-08-01

    The purpose of this article is to review recent advances in our understanding of innate lymphoid cell function and to speculate on how these cells may become activated and influence the immune response to allogeneic tissues and cells following transplantation. Innate lymphoid cells encompass several novel cell types whose wide-ranging roles in the immune system are only now being uncovered. Through cytokine production, cross-talk with both haematopoietic and nonhaematopoietic populations and antigen presentation to T cells, these cells have been shown to be key regulators in maintaining tissue integrity, as well as initiating and then sustaining immune responses. It is now clear that innate lymphoid cells markedly contribute to immune responses and tissue repair in a number of disease contexts. Although experimental and clinical data on the behaviour of these cells following transplantation are scant, it is highly likely that innate lymphoid cells will perform similar functions in the alloimmune response following transplantation and therefore may be potential therapeutic targets for manipulation to prevent allograft rejection.

  11. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  12. 'Managing' the immune system with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.

    1981-01-01

    Total lymphoid irradiation (TLI), which in the past was limited to the treatment of malignant disease, is now emerging as a practical technique in the management of unwanted immune reactions in the areas of transplant tolerance and various autoimmune diseases. Current studies are particularly promising for application of TLI in rheumatoid arthritis and lupus nephritis

  13. Innate lymphoid cells in autoimmunity: emerging regulators in rheumatic diseases

    NARCIS (Netherlands)

    Shikhagaie, Medya M.; Germar, Kristine; Bal, Suzanne M.; Ros, Xavier Romero; Spits, Hergen

    2017-01-01

    Innate lymphoid cells (ILCs) are important in the regulation of barrier homeostasis. These cells do not express T cell receptors but share many functional similarities with T helper cells and cytotoxic CD8(+) T lymphocytes. ILCs are divided into three groups, namely group 1 ILCs, group 2 ILCs and

  14. Occurrence of lymphoid cells in the intestine of the Goldfish

    NARCIS (Netherlands)

    Weinberg, Steven

    1975-01-01

    The Goldfish intestine normally contains a large number of lymphocytes, many of them being present in the epithelial layer. After stimulation with antigen, the number of lymphoid cells does not increase, but the proportion of large pyroninophilic cells and plasma cells does. It seems therefore that

  15. The uptake of radioactive iodine in rat intact Graafian follicles

    International Nuclear Information System (INIS)

    Lieberman, L.M.; Lieberman, G.L.; Lieberman, M.E.

    1984-01-01

    The concentration of iodine-131 in the ovaries of mammals has important implications in the use of I-131 for the diagnosis and treatment of thyroid disease in women. The authors studied the I-131 uptake in whole ovaries and in isolated Graafian follicles of sexually mature rats. Adult female Sprague-Dawley rats, in groups of 5-6 animals, were injected IP with 10-50 μCi of I-131, at 3, 12, and 24 hrs prior to the day of proestrus and killed on the day of proestrus. The thyroid gland and ovaries were removed intact and these organs, as well as eight other tissue specimens, were weighed. The large preovulatory follicles (6-9/ovary) were then isolated under a dissecting microscope and the remaining ovary weighed. All samples were counted in a gamma well counter and the % dose/g estimated. The thyroid gland showed 23.7% dose/organ at 24 hrs. Blood decreased from 1.6% dose/g at 3 hrs to 0.5% dose/g at 24 hrs with the uterus showing 1.1% dose/g and 0.4% dose/g at the same times. Ovarian tissue was 0.5, 0.1, and 0.1% dose/g at 3,12, and 24 hrs respectively, while the intact Graafian follicles had from one-tenth to one-third the concentration of the ovary at the same times. (0.05, 0.03, and 0.03% dose/g). The authors found that the intact Graafian follicle concentrates approximately one-thirtieth to one-sixteenth of the I-131 in the blood and one-tenth to one-third of the I-131 in the ovary. This suggests that there is no active uptake of I-131 in the follicle or follicular fluid

  16. Protein profile of mouse ovarian follicles grown in vitro.

    Science.gov (United States)

    Anastácio, Amandine; Rodriguez-Wallberg, Kenny A; Chardonnet, Solenne; Pionneau, Cédric; Fédérici, Christian; Almeida Santos, Teresa; Poirot, Catherine

    2017-12-01

    Could the follicle proteome be mapped by identifying specific proteins that are common or differ between three developmental stages from the secondary follicle (SF) to the antrum-like stage? From a total of 1401 proteins identified in the follicles, 609 were common to the three developmental stages investigated and 444 were found uniquely at one of the stages. The importance of the follicle as a functional structure has been recognized; however, up-to-date the proteome of the whole follicle has not been described. A few studies using proteomics have previously reported on either isolated fully-grown oocytes before or after meiosis resumption or cumulus cells. The experimental design included a validated mice model for isolation and individual culture of SFs. The system was chosen as it allows continuous evaluation of follicle growth and selection of follicles for analysis at pre-determined developmental stages: SF, complete Slavjanski membrane rupture (SMR) and antrum-like cavity (AF). The experiments were repeated 13 times independently to acquire the material that was analyzed by proteomics. SFs (n = 2166) were isolated from B6CBA/F1 female mice (n = 42), 12 days old, from 15 l. About half of the follicles isolated as SF were analyzed as such (n = 1143) and pooled to obtain 139 μg of extracted protein. Both SMR (n = 359) and AF (n = 124) were obtained after individual culture of 1023 follicles in a microdrop system under oil, selected for analysis and pooled, to obtain 339 μg and 170 μg of protein, respectively. The follicle proteome was analyzed combining isoelectric focusing (IEF) fractionation with 1D and 2D LC-MS/MS analysis to enhance protein identification. The three protein lists were submitted to the 'Compare gene list' tool in the PANTHER website to gain insights on the Gene Ontology Biological processes present and to Ingenuity Pathway Analysis to highlight protein networks. A label-free quantification was performed with 1D LC-MS/MS analyses to

  17. Expression patterns of porcine Toll-like receptors family set of genes (TLR1-10) in gut-associated lymphoid tissues alter with age.

    Science.gov (United States)

    Uddin, Muhammad Jasim; Kaewmala, Kanokwan; Tesfaye, Dawit; Tholen, Ernst; Looft, Christian; Hoelker, Michael; Schellander, Karl; Cinar, Mehmet Ulas

    2013-08-01

    The aim was to study the expression pattern of the porcine TLR family (TLR1-10) genes in gut-associated lymphoid tissues (GALT) of varying ages. A total of nine clinically healthy pigs of three ages group (1 day, 2 months and 5 months old) were selected for this experiment (three pigs in each group). Tissues from intestinal mucosa in stomach, duodenum, jejunum and ileum and mesenteric lymph node (MLN) were used. mRNA expression of TLRs (1-10) was detectable in all tissues and TLR3 showed the highest mRNA abundance among TLRs. TLR3 expression in stomach, and TLR1 and TLR6 expression in MLN were higher in adult than newborn pigs. The western blot results of TLR2, 3 and 9 in some cases, did not coincide with the mRNA expression results. The protein localization of TLR2, 3 and 9 showed that TLR expressing cells were abundant in the lamina propria, Peyer's patches in intestine, and around and within the lymphoid follicles in the MLN. This expressions study sheds the first light on the expression patterns of all TLR genes in GALT at different ages of pigs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Trisomy 10p and translocation of 10q to 4p associated with selective dysgenesis of IgA-producing cells in lymphoid tissue.

    Science.gov (United States)

    Saiga, Tatsuyoshi; Hashimoto, Kazuhiro; Kimura, Nobusuke; Ono, Hisako; Hiai, Hiroshi

    2007-01-01

    A combined chromosomal abberation trisomy of the short arm of chromosome 10 associated with translocation of 10q to chromosome 4p was found in a 14-month-old boy, who died after repeated bouts of pneumonia. The translocation involved the target region 4p16.3 of Wolf-Hirschhorn syndrome and/or Pitt-Rogers-Danks syndrome. The karyotype was 46,XY,der(4)t(4;10)(p16;q11.2),i(10)(p10),ish der(4)t(4;10)(p16.3;q11.2) (D4S96+,D4Z1+),i(10) (pter ++). In addition to growth retardation and external as well as internal dysmorphism, the patient had abnormalities of the immune system, such as thymic involution, generalized lymph node enlargement, unusual distribution of T cells in lymphoid follicles, and selective IgA deficiency. The IgA-producing cells were rarely found in lymph nodes but normally in intestinal mucosa. In contrast, in the lymph nodes, the paracortical T-lymphocytes were hyperplastic, but they rarely entered the primary follicles. It is assumed that the chromosomal abnormality may lead to the dysfunction of T lymphocytes and, further, to the dysgenesis of IgA-producing cells in lymph nodes but not in intestinal mucosa. This suggests that the thymus may differentially control the subsets of IgA-producing cells in lymph nodes and intestinal mucosa.

  19. Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging

    Science.gov (United States)

    Tang, Duozhuang; Tao, Si; Chen, Zhiyang; Koliesnik, Ievgen Oleksandrovich; Calmes, Philip Gerald; Hoerr, Verena; Han, Bing; Gebert, Nadja; Zörnig, Martin; Löffler, Bettina

    2016-01-01

    Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways. PMID:26951333

  20. Innate lymphoid cells are pivotal actors in allergic, inflammatory and autoimmune diseases.

    Science.gov (United States)

    Sanati, Golshid; Aryan, Zahra; Barbadi, Mehri; Rezaei, Nima

    2015-01-01

    Innate lymphoid cells (ILCs) are lymphoid cells that do not express V(D)J-rearranged receptors and play a role in the innate immune system. ILCs are categorized into three groups with respect to their function in the immune system. ILC1 induces production of IFN-γ via T-box expressed on T cells, ILC2 promotes production of type 2 cytokines via GATA-binding protein-3 and ILC3 promotes IL-17 and IL-22 production via retinoic acid receptor-related orphan receptor-γt. ILCs can maintain homeostasis in epithelial surfaces by responding to locally produced cytokines or direct recognition of danger patterns. Altered epithelial barrier function seems to be a key point in inappropriate activation of ILCs to promote inflammatory and allergic responses. ILCs play an essential role in initiation and maintenance of defense against infections as well as immune-mediated diseases. In this paper, we discuss the role of ILCs in inflammatory, allergic and autoimmune diseases.

  1. Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules.

    Science.gov (United States)

    Elemam, Noha Mousaad; Hannawi, Suad; Maghazachi, Azzam A

    2017-12-10

    Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce T H 2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation.

  2. Innate Lymphoid Cells (ILCs as Mediators of Inflammation, Release of Cytokines and Lytic Molecules

    Directory of Open Access Journals (Sweden)

    Noha Mousaad Elemam

    2017-12-01

    Full Text Available Innate lymphoid cells (ILCs are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce TH2 cytokines while ILC3s and lymphoid tissue inducer (LTis are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation.

  3. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells.

    Science.gov (United States)

    Cautivo, Kelly M; Molofsky, Ari B

    2016-06-01

    Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus. In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy AT, including those associated with type 2 or "allergic" immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, AT "browning," and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and type 2 diabetes mellitus. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines interleukin-5 and IL-13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of group 2 innate lymphoid cell cells and type 2 immunity in AT metabolism and homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

    Science.gov (United States)

    Głobińska, Anna; Kowalski, Marek L

    2017-10-01

    Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

  5. Establishment of an In Vitro System Representing the Chicken Gut-Associated Lymphoid Tissue

    Science.gov (United States)

    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a+, a majority of those emigrating onto the supporting membrane were Bu-1a− and IgM+. Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined. PMID:23185307

  6. Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Stanisavljević, S; Lukić, J; Momčilović, M; Miljković, M; Jevtić, B; Kojić, M; Golić, N; Mostarica Stojković, M; Miljković, D

    2016-06-01

    Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.

  7. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

    Directory of Open Access Journals (Sweden)

    Noorjahan Banu Alitheen

    Full Text Available The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+, a majority of those emigrating onto the supporting membrane were Bu-1a(- and IgM(+. Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240 was examined.

  8. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

    Science.gov (United States)

    Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

    2015-02-01

    Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

  9. Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Alon Peled

    2016-10-01

    Full Text Available Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs, the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter. Collectively, these observations indicate that TSPEAR plays a critical, previously unrecognized role in human tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.

  10. Targeted delivery of antigens to the gut-associated lymphoid tissues: 2. Ex vivo evaluation of lectin-labelled albumin microspheres for targeted delivery of antigens to the M-cells of the Peyer's patches.

    Science.gov (United States)

    Akande, Janet; Yeboah, Kwame G; Addo, Richard T; Siddig, Aladin; Oettinger, Carl W; D'Souza, Martin J

    2010-01-01

    The purpose of this study was to evaluate the possibility of lectin-coupled microspheres to improve the targeted delivery of protein antigens to the lymphoid tissues of mucosal surfaces. Bovine serum albumin containing acid phosphatase model protein and polystyrene microspheres were coupled with mouse M-cell-specific Ulex europaeus lectin. The coupling efficiency, physical characteristics and the binding capabilities of the microspheres to the follicle associated epithelium of the Peyer's patches were evaluated in vitro and ex vivo in mice intestine. The results showed that coupling of lectin to albumin microspheres did not significantly affect the bioactivity of the encapsulated acid phosphatase model protein. It was also shown that there was preferential binding of the lectin-coupled microspheres to the follicle-associated epithelium. It was concluded from the results of the study that coupling of ligands such as lectin specific to cells of the follicle associated epithelium can increase the targeting of encapsulated candidate antigens for delivery to the Peyer's patches of the intestine for improved oral delivery.

  11. Toxicity to nasal-associated lymphoid tissue

    NARCIS (Netherlands)

    Kuper, C.F.; Arts, J.H.E.; Feron, V.J.

    2003-01-01

    The mucosal membranes form a weak mechanical barrier, but they are provided with an extensive specific and non-specific defence system. Antigenic stimulation of the mucosal immune system of the oronasal passages induces specific, local immune responses, and activates immune components of mucosae

  12. Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

    International Nuclear Information System (INIS)

    Kokuina, Elena; Dominguez Alvarez, Carlos; Noa Pedroso, Guillermo; Martinez Rodriguez Pedro Ariel

    2009-01-01

    The common variable immunodeficiency (CVID) is the more frequent primary immunodeficiency in clinical field and its presentation forms are very variable. We describe the case of a women presenting with adult CVID with chronic diarrhea syndrome, weight loss and diffuse lymphadenopathies, where the more marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19 +) and NK cells (CD3 -C D56 +) in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20 +) and T cells (CD3 +) , similar to that of normal follicle. There was not differential expression of the K and λ light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/μL of DNA) in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID

  13. Mucosa-associated lymphoid tissue in individuals with AIDS Tecido linfoide associado à mucosa em indivíduos com AIDS

    Directory of Open Access Journals (Sweden)

    Janainna Grazielle Pacheco Olegario

    2011-06-01

    Full Text Available Vestibular folds (VF protect upper airways, but contain fewer immune cells in AIDS patients, which affects the structure of lymphoid follicles (LF. OBJECTIVE: To characterize fibrosis and immunoglobulin production in vestibular fold lymphoid tissues of AIDS patients with or with no infection and malnutrition. MATERIALS AND METHODS: A retrospective study of 71 adult vestibular fold autopsy specimens. The morphological analysis was done using the picrosirius staining method. Immunohistochemical methods consisted of anti-IgA, anti IgG, and anti IgM antibodies. RESULTS: Fibrosis was less intense in AIDS patients compared to subjects without AIDS; the same applied to patients with infection or malnutrition. IgA and IgG titers were higher in AIDS patients; IgM titers were higher in cases with infection. CONCLUSION: This study helps understand variations in lymphoid follicle components of AIDS patients; it also shows the influence of architectural changes and the effect of associated respiratory infection and malnutrition on lymphoid follicle function.Pregas vestibulares (PV são responsáveis pela proteção das vias aéreas superiores e, nos indivíduos com AIDS, apresenta diminuição das células imunes, o que influencia na estrutura dos folículos linfoides (FL. OBJETIVO: Caracterizar a fibrose e a produção de imunoglobulinas nos FL das PV nos indivíduos com AIDS, com e sem infecções e subnutrição associadas. MATERIAIS E MÉTODOS: Foi realizado um estudo retrospectivo transversal em 71 PV de adultos autopsiados. Para a análise morfológica foi usada a coloração picro-sirius. A imuno-histoquímica foi realizada com os anticorpos: anti-IgA, anti-IgG, anti-IgM. RESULTADOS: Nos pacientes com AIDS, a quantidade de fibrose foi menor quando comparados com aqueles que não possuíam AIDS, o mesmo sendo encontrado nos pacientes com infecções ou subnutrição. As quantidades de IgA e IgG foram maiores nos indivíduos com AIDS, e os valores de Ig

  14. Protein biosynthesis in isolated human scalp hair follicles.

    Science.gov (United States)

    Vermorken, A J; Weterings, P J; Bloemendal, H

    1979-02-15

    The present study demonstrates that protein biosynthesis can be studied in single isolated human scalp hair follicles. The matrix and the sheath are the main regions where amino acids are built in. Incorporation is linear for at least five hours. The newly synthesized proteins can be separated into a water-soluble, a urea-soluble and a urea-insoluble fraction. Product analysis has been performed on the first two fractions, revealing different protein patterns.

  15. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    International Nuclear Information System (INIS)

    Park, Charn Il; Han, Man Chung

    1981-01-01

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 ± 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 ± 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers

  16. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Charn Il; Han, Man Chung [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1981-06-15

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 {+-} 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 {+-} 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers.

  17. Non-coding RNAs in the Ovarian Follicle

    Directory of Open Access Journals (Sweden)

    Rosalia Battaglia

    2017-05-01

    Full Text Available The mammalian ovarian follicle is the complex reproductive unit comprising germ cell, somatic cells (Cumulus and Granulosa cells, and follicular fluid (FF: paracrine communication among the different cell types through FF ensures the development of a mature oocyte ready for fertilization. This paper is focused on non-coding RNAs in ovarian follicles and their predicted role in the pathways involved in oocyte growth and maturation. We determined the expression profiles of microRNAs in human oocytes and FF by high-throughput analysis and identified 267 microRNAs in FF and 176 in oocytes. Most of these were FF microRNAs, while 9 were oocyte specific. By bioinformatic analysis, independently performed on FF and oocyte microRNAs, we identified the most significant Biological Processes and the pathways regulated by their validated targets. We found many pathways shared between the two compartments and some specific for oocyte microRNAs. Moreover, we found 41 long non-coding RNAs able to interact with oocyte microRNAs and potentially involved in the regulation of folliculogenesis. These data are important in basic reproductive research and could also be useful for clinical applications. In fact, the characterization of non-coding RNAs in ovarian follicles could improve reproductive disease diagnosis, provide biomarkers of oocyte quality in Assisted Reproductive Treatment, and allow the development of therapies for infertility disorders.

  18. Follicle vascularity coordinates corpus luteum blood flow and progesterone production.

    Science.gov (United States)

    de Tarso, S G S; Gastal, G D A; Bashir, S T; Gastal, M O; Apgar, G A; Gastal, E L

    2017-03-01

    Colour Doppler ultrasonography was used to compare the ability of preovulatory follicle (POF) blood flow and its dimensions to predict the size, blood flow and progesterone production capability of the subsequent corpus luteum (CL). Cows (n=30) were submitted to a synchronisation protocol. Follicles ≥7mm were measured and follicular wall blood flow evaluated every 12h for approximately 3.5 days until ovulation. After ovulation, cows were scanned daily for 8 days and similar parameters were evaluated for the CL. Blood samples were collected and plasma progesterone concentrations quantified. All parameters were positively correlated. Correlation values ranged from 0.26 to 0.74 on data normalised to ovulation and from 0.31 to 0.74 on data normalised to maximum values. Correlations between calculated ratios of both POF and CL in data normalised to ovulation and to maximum values ranged from moderate (0.57) to strong (0.87). Significant (Pprogesterone concentrations of the resultant CL. These findings indicate that follicle vascularity coordinates CL blood flow and progesterone production in synchronised beef cows.

  19. Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential.

    Science.gov (United States)

    Galat, Yekaterina; Dambaeva, Svetlana; Elcheva, Irina; Khanolkar, Aaruni; Beaman, Kenneth; Iannaccone, Philip M; Galat, Vasiliy

    2017-03-17

    The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification. Thus, it has been shown that variations in cytokine and inhibitory molecule treatments in the first few days of hematopoietic differentiation define primitive versus definitive potential of produced hematopoietic progenitor cells. The majority of current feeder-free, defined systems for hematopoietic induction from pluripotent stem cells include prolonged incubations with various cytokines that make the differentiation process complex and time consuming. We established that the application of Wnt agonist CHIR99021 efficiently promotes differentiation of human pluripotent stem cells in the absence of any hematopoietic cytokines to the stage of hemogenic endothelium capable of definitive hematopoiesis. The hemogenic endothelium differentiation was accomplished in an adherent, serum-free culture system by applying CHIR99021. Hemogenic endothelium progenitor cells were isolated on day 5 of differentiation and evaluated for their endothelial, myeloid, and lymphoid potential. Monolayer induction based on GSK3 inhibition, described here, yielded a large number of CD31 + CD34 + hemogenic endothelium cells. When isolated and propagated in adherent conditions, these progenitors gave rise to mature endothelium. When further cocultured with OP9 mouse stromal cells, these progenitors gave rise to various cells of myeloid lineages as well as natural killer lymphoid, T-lymphoid

  20. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

    Science.gov (United States)

    Melo-Gonzalez, Felipe; Hepworth, Matthew R

    2017-03-01

    Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.

  1. Clinical outcomes of childhood x-irradiation for lymphoid hyperplasia

    International Nuclear Information System (INIS)

    Pottern, L.M.

    1987-01-01

    A prospective study was conducted to explore the relationship between childhood x-irradiation for lymphoid hyperplasia and the subsequent development of thyroid gland and other head and neck disorders. All individuals under 18 years of age who were x-irradiated for lymphoid hyperplasia during the years 1938-69 at Children's Hospital Medical Center, Boston comprised the exposed population. The comparison group consisted of non-exposed, surgically treated individuals. The study included a health questionnaire and a clinical examination component. A history of thyroid cancer was reported by 11 exposed subjects and no non-exposed subjects. Significantly elevated standardized incidence ratios of thyroid cancer were seen for both exposed males and females, 19.9 and 12.1, respectively. The average thyroid radiation dose was 25.8 rads and the mean latency period was 17.3 years

  2. Total lymphoid irradiation in refractory systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.

    1986-01-01

    In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental

  3. Beyond NK cells: the expanding universe of innate lymphoid cells.

    Science.gov (United States)

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  4. Beyond NK cells: the expanding universe of Innate Lymphoid Cells.

    Directory of Open Access Journals (Sweden)

    Marina eCella

    2014-06-01

    Full Text Available For a long time NK cells were thought to be the only immune innate lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different Innate Lymphoid Cells found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. ILC populations closely mirror the phenotype of adaptive Thelper subsets in their ability to secrete soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response appropriate to the incoming insult. Here we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  5. The Common Follicle-Stimulating Hormone Receptor (FSHR) Promoter Polymorphism FSHR -29G > A Affects Androgen Production in Normal Human Small Antral Follicles

    DEFF Research Database (Denmark)

    Borgbo, Tanni; Klučková, Hana; Macek, Milan

    2017-01-01

    ) FSHR -29G > A (rs1394205) on hormonal conditions in humsan small antral follicles (hSAFs) obtained from women in the natural menstrual cycle. This study investigated the follicle fluid (FF) concentrations of anti-Müllerian hormone, estradiol, progesterone, androstenedione, and testosterone in h...

  6. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-05-15

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  7. Total lymphoid irradiation in the Wistar rat: technique and dosimetry

    International Nuclear Information System (INIS)

    Hoogenhout, J.; Kazem, I.; de Jong, J.

    1983-01-01

    The technical and dosimetric aspects of total lymphoid irradiation (TLI) in the Wistar rat were evaluated as part of a set-up to develop a new model for tumor xenotransplantation. Information obtained from anatomical dissections, radionuclide imaging of the spleen, lymphography and chromolymphography was used to standardize the localization portals cut out in a lead plate. The two portals encompassed the lymphoid tissue above and below the diaphragm. A specially designed masonite phantom was used to measure the dose distribution in the simulated target volumes. Ionization chamber dosimetery, thermoluminescence dosimetry and film densitometry were used for measuring exposure and absorbed dose. Irradiation was performed with 250 kV X rays (HVL 3.1 mm Cu). The dose rate was regulated by adjusting the treatment distance. The dose inhomogeneity measured in the target volumes varied between 80-100%. The side scatter dose to non target tissues under the shielded area between the two portals ranged between 20-30%. The technique and dosimetry of total lymphoid irradiation in Wistar rats are now standardized and validated and pave the way for tumor xenotransplantation experiments

  8. Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency.

    Science.gov (United States)

    Maglione, Paul J; Cols, Montserrat; Cunningham-Rundles, Charlotte

    2017-10-05

    Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches.

  9. Human natural killer cell development in secondary lymphoid tissues

    Science.gov (United States)

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  10. Treatment of intractable lupus nephritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-01-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis

  11. The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation

    DEFF Research Database (Denmark)

    Klose, Christoph S N; Mahlakõiv, Tanel; Moeller, Jesper B

    2017-01-01

    The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have important roles in stimulating innate and adaptive immune responses that are required for resistance to helminth infection, promotion of allergic inflammation, metabolic homeostasis and tissue repair. Group 2 innate lymphoid cells......-localize with cholinergic neurons that express the neuropeptide neuromedin U (NMU). In contrast to other haematopoietic cells, ILC2s selectively express the NMU receptor 1 (NMUR1). In vitro stimulation of ILC2s with NMU induced rapid cell activation, proliferation, and secretion of the type 2 cytokines IL-5, IL-9 and IL-13...... that was dependent on cell-intrinsic expression of NMUR1 and Gαq protein. In vivo administration of NMU triggered potent type 2 cytokine responses characterized by ILC2 activation, proliferation and eosinophil recruitment that was associated with accelerated expulsion of the gastrointestinal nematode Nippostrongylus...

  12. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue

    OpenAIRE

    Martinet , Kim ,; Bloquet , Stéphane; Bourgeois , Christine

    2014-01-01

    International audience; BackgroundCD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue ...

  13. Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development.

    Science.gov (United States)

    Merchant, Hamid A; McConnell, Emma L; Liu, Fang; Ramaswamy, Chandrasekaran; Kulkarni, Rucha P; Basit, Abdul W; Murdan, Sudaxshina

    2011-01-18

    Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4-7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51g, 153g and 1546g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig>rabbit>pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pigpig). The lymphoid tissue distribution (lymphoid follicles, Peyer's patches and long strips) along the length of the gut in these animals is presented; in particular, an abundance of lymphoid tissue was found in pig's stomach, small intestine and caecum, and rabbit's appendix. Their ample presence indicated the potential utility of these animal species in oral and colonic vaccination. These differences in the gastrointestinal parameters of the guinea pig, rabbit and pig reiterates the crucial importance of correctly selecting animal models for pre-clinical studies. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Modulation of cultured porcine granulosa cell responsiveness to follicle stimulating hormone and epidermal growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Buck, P.A.

    1986-01-01

    Ovarian follicular development is dependent upon the coordinated growth and differentiation of the granulosa cells which line the follicle. Follicle stimulating hormone (FSH) induces granulosa cell differentiation both in vivo and in vitro. Epidermal growth factor (EGF) stimulates granulosa cell proliferation in vitro. The interaction of these two effectors upon selected parameters of growth and differentiation was examined in monolayer cultures of porcine granulose cells. Analysis of the EGF receptor by /sup 125/I-EGF binding revealed that the receptor was of high affinity with an apparent dissociation constant of 4-6 x 10/sup -10/ M. The average number of receptors per cell varied with the state of differentiation both in vivo and in vitro; highly differentiated cells bound two-fold less /sup 125/I-EGF and this effect was at least partially induced by FSH in vitro. EGF receptor function was examined by assessing EGF effects on cell number and /sup 3/H-thymidine incorporation. EGF stimulated thymidine incorporation in both serum-free and serum-supplemented culture, but only in serum-supplemented conditions was cell number increased. EGF receptor function was inversely related to the state of differentiation and was attenuated by FSH. The FSH receptor was examined by /sup 125/I-FSH binding. EGF increased FSH receptor number, and lowered the affinity of the receptor. The function of these receptors was assessed by /sup 125/I-hCG binding and progesterone radioimmunoassay. If EGF was present continuously in the cultures. FSH receptor function was attenuated regardless of FSH receptor number. A preliminary effort to examine the mechanism of this interaction was performed by analyzing hormonally controlled protein synthesis with /sup 35/S-methionine labeling, SDS polyacrylamide gel electrophoresis and fluorography. FSH promoted the expression of a 27,000 dalton protein. This effect was attenuated by EGF.

  15. The Hair Follicle: An Underutilized Source of Cells and Materials for Regenerative Medicine.

    Science.gov (United States)

    Kiani, Mehrdad T; Higgins, Claire A; Almquist, Benjamin D

    2018-04-09

    The hair follicle is one of only two structures within the adult body that selectively degenerates and regenerates, making it an intriguing organ to study and use for regenerative medicine. Hair follicles have been shown to influence wound healing, angiogenesis, neurogenesis, and harbor distinct populations of stem cells; this has led to cells from the follicle being used in clinical trials for tendinosis and chronic ulcers. In addition, keratin produced by the follicle in the form of a hair fiber provides an abundant source of biomaterials for regenerative medicine. In this review, we provide an overview of the structure of a hair follicle, explain the role of the follicle in regulating the microenvironment of skin and the impact on wound healing, explore individual cell types of interest for regenerative medicine, and cover several applications of keratin-based biomaterials.

  16. Association of versican with dermal matrices and its potential role in hair follicle development and cycling

    DEFF Research Database (Denmark)

    du Cros, D L; LeBaron, R G; Couchman, J R

    1995-01-01

    Versican is a member of the group of aggregating proteoglycans involved in matrix assembly and structure and in cell adhesion. We examined changes in the distribution of versican in mammalian skin, with emphasis on hair follicle development and cycling. In adult human skin, immunostaining...... for versican appeared predominantly in the dermis, with intense staining of the reticular dermis. Weak staining was observed at the dermoepidermal junction and the connective tissue sheath of hair follicles. Versican expression was also noted in the reticular dermis of rat skin, within dermal papillae......, and possibly associated with follicle basement membranes. During mouse hair follicle development, versican was not expressed until the hair follicles were beginning to produce fibers. With follicle maturation, versican expression intensified in the dermal papillae, reaching a maximum at the height...

  17. PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer.

    Science.gov (United States)

    Davenport, Kristen A; Hoover, Clare E; Bian, Jifeng; Telling, Glenn C; Mathiason, Candace K; Hoover, Edward A

    2017-01-01

    The agent responsible for prion diseases is a misfolded form of a normal protein (PrPC). The prion hypothesis stipulates that PrPC must be present for the disease to manifest. Cervid populations across the world are infected with chronic wasting disease, a horizontally-transmissible prion disease that is likely spread via oral exposure to infectious prions (PrPCWD). Though PrPCWD has been identified in many tissues, there has been little effort to characterize the overall PrPC expression in cervids and its relationship to PrPCWD accumulation. We used immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay to describe PrPC expression in naïve white-tailed deer. We used real-time, quaking-induced conversion (RT-QuIC) to detect prion seeding activity in CWD-infected deer. We assessed tissues comprising the alimentary tract, alimentary-associated lymphoid tissue and systemic lymphoid tissue from 5 naïve deer. PrPC was expressed in all tissues, though expression was often very low compared to the level in the CNS. IHC identified specific cell types wherein PrPC expression is very high. To compare the distribution of PrPC to PrPCWD, we examined 5 deer with advanced CWD infection. Using RT-QuIC, we detected prion seeding activity in all 21 tissues. In 3 subclinical deer sacrificed 4 months post-inoculation, we detected PrPCWD consistently in alimentary-associated lymphoid tissue, irregularly in alimentary tract tissues, and not at all in the brain. Contrary to our hypothesis that PrPC levels dictate prion accumulation, PrPC expression was higher in the lower gastrointestinal tissues than in the alimentary-associated lymphoid system and was higher in salivary glands than in the oropharyngeal lymphoid tissue. These data suggest that PrPC expression is not the sole driver of prion accumulation and that alimentary tract tissues accumulate prions before centrifugal spread from the brain occurs.

  18. Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.

    Science.gov (United States)

    Nagashima, Kazuki; Sawa, Shinichiro; Nitta, Takeshi; Prados, Alejandro; Koliaraki, Vasiliki; Kollias, George; Nakashima, Tomoki; Takayanagi, Hiroshi

    2017-11-04

    The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells. In order to investigate MCi cells more extensively, it will be necessary to develop experimental tools in addition to the Twist2-Cre driver mice and characterize such drivers in specificity and efficiency. Here we show that M cell differentiation and IgA production are impaired in the targeted deletion of RANKL by the Col6a1-Cre driver. We compared Col6a1-Cre with Twist2-Cre in terms of the specificity for mesenchymal cells in GALTs. Col6a1-Cre CAG-CAT-EGFP mice exhibited EGFP expression in podoplanin + CD31 - cells including MCi cells, while Twist2-Cre mice were shown to target endothelial cells and podoplanin + CD31 - cells. Tnfsf11 fl/Δ Col6a1-Cre mice exhibited the absence of M cells and severe IgA reduction together with an alteration in gut microbial composition. Moreover, we analyzed germ free mice to test whether changes in the microbiota are the cause of M cell deficiency. M cell differentiation was normal in the CPs/ILFs of germ free mice, indicating that MCi cells induce M cells independently of microbial colonization. This study demonstrates that Col6a1-Cre driver mice are as useful as Twist2-Cre driver mice for functional analyses of GALT-resident mesenchymal cells, including MCi cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves

    OpenAIRE

    Amoh, Yasuyuki; Li, Lingna; Campillo, Raul; Kawahara, Katsumasa; Katsuoka, Kensei; Penman, Sheldon; Hoffman, Robert M.

    2005-01-01

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, also is expressed in follicle stem cells and their immediate, differentiated progeny. The fluorescent protein GFP, whose expression is driven by the nestin regulatory element in transgenic mice, served to mark the follicle cell fate. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34 but ne...

  20. Regulation and mechanism of leptin on lipid metabolism in ovarian follicle cells from yellow catfish Pelteobagrus fulvidraco.

    Science.gov (United States)

    Zhang, Li-Han; Tan, Xiao-Ying; Wu, Kun; Zhuo, Mei-Qin; Song, Yu-Feng; Chen, Qing-Ling

    2015-10-01

    The present study was conducted to determine the effect of leptin on lipid metabolism in ovarian follicle cells of yellow catfish Pelteobagrus fulvidraco. For that purpose, primary ovarian follicle cells were isolated from yellow catfish, cultured and subjected to different treatments (control, 0.1% DMSO, 500ng/ml leptin, 500ng/ml leptin plus 100μM wortmannin, 500ng/ml leptin plus 50nM AG490, respectively) for 48h. Intracellular triglyceride (TG) content, the activities (CPT I, FAS, G6PD, and 6PGD) and/or expression level of several enzymes (CPT I, FAS, G6PD, 6PGD, ACCa and ACCb), as well as the mRNA expression of transcription factors (PPARα, PPARγ and SREBP-1) involved in lipid metabolism were determined. Recombinant human leptin (rt-hLEP) incubation significantly reduced intracellular TG content, activities and mRNA levels of FAS, G6PD and 6PGD, SREBP-1 and PPARγ, but enhanced activity and mRNA level of CPT I, PPARα and ACCa. Specific inhibitors AG490 and wortmannin of JAK-STAT and IRS-PI3K signaling pathways prevented leptin-induced changes, indicating that JAK-STAT and IRS-PI3K signaling pathways were involved in the process of leptin-induced changes of lipid metabolism. Based on these observations above, for the first time, our study indicated that leptin reduced lipid deposition by activating lipolysis and suppressing lipogenesis in ovarian follicles of yellow catfish, and both JAK-STAT and IRS-PI3K signaling pathways were involved in the changes of leptin-induced lipid metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Anti-Müllerian hormone inhibits activation and growth of bovine ovarian follicles in vitro and is localized to growing follicles.

    Science.gov (United States)

    Yang, M Y; Cushman, R A; Fortune, J E

    2017-05-01

    Does anti-Müllerian hormone (AMH) inhibit activation (initiation of growth) of primordial follicles and attenuate the growth of primary follicles in cattle, an excellent animal model for human ovarian follicular development? AMH inhibited activation of bovine primordial follicles and attenuated the growth of activated follicles in vitro. In mice null mutant for AMH, the pool of primordial follicles is depleted prematurely and AMH inhibits follicle activation in vitro. Results of studies with human ovarian tissue in vitro were inconsistent. Our previous work provided indirect evidence that AMH inhibits follicle activation in bovine ovaries. Pieces of fetal bovine ovarian cortex (2 pieces/culture well), obtained during mid or late pregnancy, were cultured in control medium or with graded doses of AMH for 2, 10 or 12 days. Effects of treatment on follicle activation and growth were determined by histological morphometry; follicles in every 20th histological section were staged (primordial or primary), counted, and measured. In addition, AMH was immunolocalized in bovine ovaries obtained at various times during pregnancy (n = 20 ovaries). Bovine fetal ovaries at mid or late gestation were obtained at a commercial abattoir. Pieces of ovarian cortex were cultured without or with AMH and fixed for histological morphometry on Day 0 and at the end of culture. Treatments were applied to duplicate cultures from each of two or three fetuses. In 12-day cultures, addition of AMH was delayed until the third day. Histological analysis provided information about the types, numbers and sizes of follicles in cortical pieces before and after treatments. Ovaries obtained during the second and third trimesters were assessed for the presence of AMH by immunohistochemistry. AMH (100-500 ng/ml) inhibited follicle activation in response to an activator (insulin) in ovarian cortical pieces from fetal ovaries in late gestation. Dose-dependent inhibitory effects on the diameters of primary

  2. Does AMH Reflect Follicle Number Similarly in Women with and without PCOS?

    Directory of Open Access Journals (Sweden)

    Sverre C Christiansen

    Full Text Available Increased Anti-Mullerian Hormone in polycystic ovary syndrome, may be due to overactive follicles rather than reflect antral follicle count.Does Anti-Mullerian Hormone reflect antral follicle count similarly in women with or without polycystic ovary syndrome or polycystic ovarian morphology?Cross-sectional, case-control.Women who delivered preterm in 1999-2006. For each index woman, a woman with a term delivery was identified.Participation rate was 69%. Between 2006-2008, 262 women were included, and diagnosed to have polycystic ovary syndrome, polycystic ovarian morphology or to be normal controls.Blood tests, a clinical examination and vaginal ultrasound.Anti-Mullerian Hormone/antral follicle count-ratio, SHBG, androstenedione and insulin, to test potential influence on the Anti-Mullerian Hormone/antral follicle count -ratio.Mean Anti-Mullerian Hormone/antral follicle count ratio in women with polycystic ovary syndrome or polycystic ovarian morphology was similar to that of the controls (polycystic ovary syndrome: 1,2 p = 0,10 polycystic ovarian morphology: 1,2, p = 0,27 Controls 1,3. Anti-Mullerian Hormone showed a positive linear correlation to antral follicle count in all groups. Multivariate analysis did not change the results.We confirmed the positive correlation between AMH and follicle count. Anti-Mullerian Hormone seems to be a reliable predictor of antral follicle count, independent of polycystic ovary syndrome diagnosis or ovarian morphology.

  3. Should we isolate human preantral follicles before or after cryopreservation of ovarian tissue?

    Science.gov (United States)

    Vanacker, Julie; Luyckx, Valérie; Amorim, Christiani; Dolmans, Marie-Madeleine; Van Langendonckt, Anne; Donnez, Jacques; Camboni, Alessandra

    2013-04-01

    To evaluate the survival and growth potential of human preantral follicles isolated before and after cryopreservation. Pilot study. Gynecology research unit in a university hospital. Six women aged 27 to 32 years. Six ovarian biopsy samples were cut into two equal parts, half subjected to slow-freezing followed by follicle isolation (cryo-iso group) and alginate-matrigel embedding, and half immediately processed for follicle isolation and alginate-matrigel embedding followed by slow-freezing (iso-cryo group) or used as fresh controls (fresh group). Follicle number, viability, diameter, and morphology. After 1,134 preantral follicles had been isolated from fresh biopsy samples and 1,132 from frozen specimens, the three groups were compared before and after 7 days of in vitro culture (IVC) in alginate-matrigel beads. No statistically significant differences in viability were found between the three groups before or after IVC, but follicle diameter increased in all three groups after IVC. Morphology analysis revealed well-preserved follicles in both the iso-cryo and cryo-iso groups after IVC. Human preantral follicles can be successfully cryopreserved before or after isolation without impairing their ability to survive and grow in vitro. This could lead to development of new protocols for follicle cryopreservation, IVC, and grafting in clinical and research settings for fertility preservation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Proteomic Analysis of Fetal Ovaries Reveals That Primordial Follicle Formation and Transition Are Differentially Regulated

    Directory of Open Access Journals (Sweden)

    Mengmeng Xu

    2017-01-01

    Full Text Available Primordial follicle formation represents a critical phase of the initiation of embryonic reproductive organ development, while the primordial follicle transition into primary follicle determines whether oestrus or ovulation will occur in female animals. To identify molecular mechanism of new proteins which are involved in ovarian development, we employed 2D-DIGE to compare the protein expression profiles of primordial follicles and primary follicles of fetal ovaries in pigs. Fetal ovaries were collected at distinct time-points of the gestation cycle (g55 and g90. The identified proteins at the g55 time-point are mainly involved in the development of anatomical structures [reticulocalbin-1 (RCN1, reticulocalbin-3 (RCN3], cell differentiation (actin, and stress response [heterogeneous nuclear ribonucleoprotein K (HNRNPK]. Meanwhile, at the g90 stage, the isolated proteins with altered expression levels were mainly associated with cell proliferation [major vault protein (MVP] and stress response [heat shock-related 70 kDa protein 2 (HSPA2]. In conclusion, our work revealed that primordial follicle formation is regulated by RCN1, RCN3, actin, and HNRNPK, while the primordial follicle transformation to primary follicle is regulated by MVP and HSPA2. Therefore, our results provide further information for the prospective understanding of the molecular mechanism(s involved in the regulation of the ovarian follicle development.

  5. Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes

    DEFF Research Database (Denmark)

    Brakebusch, C; Grose, R; Quondamatteo, F

    2000-01-01

    developed severe hair loss due to a reduced proliferation of hair matrix cells and severe hair follicle abnormalities. Eventually, the malformed hair follicles were removed by infiltrating macrophages. The epidermis of the back skin became hyperthickened, the basal keratinocytes showed reduced expression......, the integrity of the basement membrane surrounding the beta 1-deficient hair follicle was not affected. Finally, the dermis became fibrotic. These results demonstrate an important role of beta 1 integrins in hair follicle morphogenesis, in the processing of basement membrane components, in the maintenance...

  6. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

    Science.gov (United States)

    Humby, Frances; Bombardieri, Michele; Manzo, Antonio; Kelly, Stephen; Blades, Mark C; Kirkham, Bruce; Spencer, Jo; Pitzalis, Costantino

    2009-01-13

    Follicular structures resembling germinal centres (GCs) that are characterized by follicular dendritic cell (FDC) networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA). However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i) express activation-induced cytidine deaminase (AID), the enzyme required for somatic hypermutation and class-switch recombination (CSR) of Ig genes; (ii) support ongoing CSR and ACPA production; and (iii) remain functional in a RA/severe combined immunodeficiency (SCID) chimera model devoid of new immune cell influx into the synovium. Using immunohistochemistry (IHC) and quantitative Taqman real-time PCR (QT-PCR) in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching) was observed in synovial grafts expressing FDCs/CD21L. Furthermore, synovial mRNA levels of AID were

  7. The hair follicle bulge: a niche for adult stem cells.

    Science.gov (United States)

    Pasolli, Hilda Amalia

    2011-08-01

    Adult stem cells (SCs) are essential for tissue homeostasis and wound repair. They have the ability to both self-renew and differentiate into multiple cell types. They often reside in specialized microenvironments or niches that preserve their proliferative and tissue regenerative capacity. The murine hair follicle (HF) has a specialized and permanent compartment--the bulge, which safely lodges SCs and provides the necessary molecular cues to regulate their function. The HF undergoes cyclic periods of destruction, regeneration, and rest, making it an excellent system to study SC biology.

  8. Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies.

    Science.gov (United States)

    Colvin, Kelley L; Cripe, Patrick J; Ivy, D Dunbar; Stenmark, Kurt R; Yeager, Michael E

    2013-11-01

    Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1(+) high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.

  9. Skin-associated lymphoid tissues (SALT): origins and functions

    International Nuclear Information System (INIS)

    Streilein, J.W.

    1983-01-01

    The skin has an unusual set of immunologic requirements. It is confronted by a specialized set of pathogenic organisms and environmental chemicals that represent a distinctive spectrum of antigenic specificities. Skin is subjected to physicochemical stresses such as irradiation with ultraviolet light that alter dramatically its immunologic properties. It is proposed that nature has provided skin with a unique collection of lymphoid cells, reticular cells, and organized lymphoid organs to deal with these special demands. Evidence in favor of the existence of skin-associated lymphoid tissues (SALT) includes (1) the cutaneous microenvironment is capable on its own of accepting, processing, and presenting nominal antigen; (2) strategically located peripheral lymph nodes are able to accept immunogenic signals derived from skin; (3) subsets of T lymphocytes display differential affinity for skin and its associated peripheral nodes; and (4) acquisition of this affinity by T cells is determined at least in part by differentiation signals received in situ from resident cutaneous cells. Responsibility for the establishment and integration of SALT rests with keratinocytes, Langerhans cells, and immunocompetent lymphocytes, each of which contributes uniquely to the synthesis. Together they provide skin with immune surveillance that effectively prejudices against the development of cutaneous neoplasms and persistent infection with intracellular pathogens. In patients who have been under long-term immunosuppressive therapy, the large majority of nonlymphoid malignancies arise within the skin, rather than other types of tissues. These data suggest that immune surveillance, once thought to be an immune defense operative in all somatic tissues, is a specialized immune function dedicated to the skin and mediated by SALT

  10. Anti-Müllerian hormone, follicle stimulating hormone, antral follicle count, and risk of menopause within 5 years.

    Science.gov (United States)

    Kim, Catherine; Slaughter, James C; Wang, Erica T; Appiah, Duke; Schreiner, Pamela; Leader, Benjamin; Calderon-Margalit, Ronit; Sternfeld, Barbara; Siscovick, David; Wellons, Melissa

    2017-08-01

    To evaluate the ability of concentration of anti-Müllerian hormone (AMH), antral follicle count (AFC), and concentration of follicle stimulating hormone (FSH) to predict the onset of menopause. The Coronary Artery Risk Development in Young Adults Study (CARDIA) Women's Study was an ancillary study to CARDIA, a population-based study of adults aged 18-30 years followed for 3 decades. For this report, participants were women (n=426) who had attended the CARDIA year 15-16 (2000-2001) examination, had at least one ovary, were not pregnant, and underwent serum AMH and FSH measurement and transvaginal ultrasonography in 2002-2003. The probability of menopause in 5 years based upon AMH, FSH, and AFC. The mean age of the women at the time of AMH, FSH, and AFC assessment was 43 years. The cumulative incidence of menopause at 25 years (or follow-up) was 27% (n=426), and the incidence within 5 years was 13% (n=55). Among women aged 45-49 years, undetectable AMH concentrations were associated with a greater than 60% probability of menopause within 5 years, whereas approximately 1/3 of women with no or just one antral follicle experienced menopause within 5 years. Both low and high concentrations of FSH were associated with greater odds of menopause than intermediate concentrations. Models with multiple markers did not improve the prediction of menopause over that afforded by models with single markers. The ability to predict onset of menopause was improved with any of the three menopausal markers in addition to age. AMH concentrations were more closely associated with menopause than AFC or FSH. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Isolation and characterization of mouse innate lymphoid cells.

    Science.gov (United States)

    Halim, Timotheus Y F; Takei, Fumio

    2014-08-01

    Innate lymphoid cells (ILCs) are rare populations of cytokine-producing lymphocytes and are divided into three groups, namely ILC1, ILC2, and ILC3, based on the cytokines that they produce. They comprise less than 1% of lymphocytes in mucosal tissues and express no unique cell surface markers. Therefore, they can only be identified by combinations of multiple cell surface markers and further characterized by cytokine production in vitro. Thus, multicolor flow cytometry is the only reliable method to purify and characterize ILCs. Here we describe the methods for cell preparation, flow cytometric analysis, and purification of murine ILC2 and ILC3. Copyright © 2014 John Wiley & Sons, Inc.

  12. Effect of total lymphoid irradiation in chronic progressive multiple sclerosis

    International Nuclear Information System (INIS)

    Cook, S.D.; Devereux, C.; Troiano, R.; Hafstein, M.P.; Zito, G.; Hernandez, E.; Lavenhar, M.; Vidaver, R.; Dowling, P.C.

    1986-01-01

    Total lymphoid irradiation (TLI; 1980 cGy) or sham irradiation was given to 40 patients with chronic progressive multiple sclerosis (MS) in a prospective, randomised, double-blind study. During mean follow-up of 21 months, MS patients treated with TLI has less functional decline than sham-irradiated MS patients (p<0.01). A significant relation was noted between absolute blood lymphocyte counts in