Effects of PARP-1 Deficiency on Th1 and Th2 Cell Differentiation

Directory of Open Access Journals (Sweden)

M. Sambucci

2013-01-01

Full Text Available T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosylation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose polymerases (PARPs. Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4+ cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ+ cells as well as IFN-γ production, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases.

Preferential susceptibility of Th9 and Th2 CD4+ T cells to X4-tropic HIV-1 infection.

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Orlova-Fink, Nina; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

2017-10-23

The functional polarization of CD4 T cells determines their antimicrobial effector profile, but may also impact the susceptibility to infection with HIV-1. Here, we analyzed the susceptibility of CD4 T cells with different functional polarization to infection with X4 and R5-tropic HIV-1. CD4 T cells with a Th1, Th2, Th17, and Th9 polarization were subjected to in-vitro infection assays with X4, R5, or vesicular stomatitis virus-G protein-pseudotyped HIV-1. In addition, we sorted differentially polarized CD4 T-cell subsets from individuals treated with antiretroviral therapy and analyzed the tropism of viral env sequences. Th9-polarized CD4 T cells and, to a lesser extent, Th2-polarized CD4 T cells expressed higher surface levels of CXCR4, and are more permissive to X4-tropic infection in vitro. In contrast, Th1 and Th17 CD4 T cells exhibited stronger surface expression of CCR5, and were more susceptible to infection with R5-tropic viruses. Correspondingly, the distribution of X4-tropic viral sequences in antiretroviral therapy-treated HIV-1-infected patients was biased toward Th9/Th2 cells, whereas R5-tropic sequences were more frequently observed in Th17 cells. CD4 T-cell polarization is associated with a distinct susceptibility to X4 and R5-tropic HIV-1 infection.

CpG Oligodeoxynucleotides Enhance the Efficacy of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes by Modifying the Th1 Polarization and Local Infiltration of Th17 Cells

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Lin Xu

2010-01-01

Full Text Available Adoptive cell transfer immunotherapy using tumor infiltrating lymphocytes (TILs was an important therapeutic strategy against tumors. But the efficacy remains limited and development of new strategies is urgent. Recent evidence suggested that CpG-ODNs might be a potent candidate for tumor immunotherapy. Here we firstly reported that CpG-ODNs could significantly enhance the antitumor efficacy of adoptively transferred TILs in vivo accompanied by enhanced activity capacity and proliferation of CD8+ T cells and CD8+ T cells, as well as a Th1 polarization immune response. Most importantly, we found that CpG-ODNs could significantly elevate the infiltration of Th17 cells in tumor mass, which contributed to anti-tumor efficacy of TILs in vivo. Our findings suggested that CpG ODNs could enhance the anti-tumor efficacy of adoptively transferred TILs through modifying Th1 polarization and local infiltration of Th17 cells, which might provide a clue for developing a new strategy for ACT based on TILs.

Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses

DEFF Research Database (Denmark)

Litjens, Nicolle H R; Rademaker, Mirjam; Ravensbergen, Bep

2004-01-01

Psoriasis vulgaris, a type-1 cytokine-mediated chronic skin disease, can be treated successfully with fumaric acid esters (FAE). Beneficial effects of this medication coincided with decreased production of IFN-gamma. Since dendritic cells (DC) regulate the differentiation of T helper (Th) cells......% of that by the respective Th cells cocultured with control DC. IL-4 production by primed, but not naive Th cells cocultured with MMF-DC was decreased as compared to cocultures with control DC. IL-10 production by naive and primed Th cells cocultured with MMF-DC and control DC did not differ. In addition, MMF inhibited LPS......-induced NF-kappaB activation in DC. Together, beneficial effects of FAE in psoriasis involve modulation of DC polarization by MMF such that these cells down-regulate IFN-gamma production by Th cells....

Polar-Direct-Drive Experiments on OMEGA

International Nuclear Information System (INIS)

Marshall, F.J.; Craxton, R.S.; Bonino, M.J.; Epstein, R.; Glebov, V.Yu.; Jacobs-Perkins, D.; Knauer, J.P.; Marozas, J.A.; McKenty, P.W.; Noyes, S.G.; Radha, P.B.; Seka, W.; Skupsky, S.; Smalyuk

2006-01-01

Polar direct drive (PDD), a promising ignition path for the NIF while the beams are in the indirect-drive configuration, is currently being investigated on the OMEGA laser system by using 40 beams in six rings repointed to more uniformly illuminate the target. The OMEGA experiments are being performed with standard, ''warm'' targets with and without the use of an equatorial ''Saturn-like'' toroidally shaped CH ring. Target implosion symmetry is diagnosed with framed x-ray backlighting using additional OMEGA beams and by time-integrated x-ray imaging of the stagnating core

Preparing for polar-drive ignition on the National Ignition Facility

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McKenty P.W.

2013-11-01

Full Text Available The implementation of polar drive (PD at the National Ignition Facility (NIF will enable the execution of direct-drive implosions while the facility is configured for x-ray drive. The Laboratory for Laser Energetics (LLE, in collaboration with LLNL, LANL and GA, is implementing PD on the NIF. LLE has designed and participates in the use of PD implosions for diagnostic commissioning on the NIF. LLE has an active experimental campaign to develop PD in both warm and cryogenic target experiments on OMEGA. LLE and its partners are developing a Polar Drive Project Execution Plan, which will provide a detailed outline of the requirements, resources, and timetable leading to PD-ignition experiments on the NIF.

In vitro Th1 and Th2 cell polarization is severely influenced by the initial ratio of naïve and memory CD4+ T cells

DEFF Research Database (Denmark)

Blom, Lars; Poulsen, Lars K.

2013-01-01

by even small percentages (99% naïve CD4+ T cells resulted in better Th1 and Th2 polarization with significant reduced fractions of IL-4+ and IFN-γ+ CD4+ T cells, respectively. Moreover, the Th2 primed >99% naïve CD4+ T cells showed significantly higher ratio of IL-4+:IFN-γ+ (>4 fold) and GATA-3:+T......-bet+ (>3 fold) CD4+ T cells when compared with the standard purified >90-95% naïve CD4+ T cells primed under the same culture conditions. This suggests immunomagnetic bead separation, a low cost and easy available technique, with few modifications to the manufacturer's protocol as an attractive alternative...... for laboratories not having a cell sorter. Taken together, we report that it is essential to use rigorously purified (>99%) naïve CD4+ T cells for optimal initial in vitro Th1 and Th2 priming....

Mycobacterium tuberculosislpdC, Rv0462, induces dendritic cell maturation and Th1 polarization

Energy Technology Data Exchange (ETDEWEB)

Heo, Deok Rim [Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Shin, Sung Jae; Kim, Woo Sik [Department of Microbiology, College of Medicine, Chungnam National University, Munwha-Dong, Jung-Ku, Daejeon 301-747 (Korea, Republic of); Noh, Kyung Tae; Park, Jin Wook; Son, Kwang Hee [Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Park, Won Sun [Department of Physiology, Kangwon National University, School of Medicine, Chuncheon 200-701 (Korea, Republic of); Lee, Min-Goo [Department of Physiology, Korea University, College of Medicine, Anam-dong, Sungbuk-Gu, Seoul 136-705 (Korea, Republic of); Kim, Daejin [Department of Anatomy, Chung-Ang University, College of Medicine, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Shin, Yong Kyoo [Department of Pharmacology, Chung-Ang University, College of Medicine, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Jung, In Duk, E-mail: jungid@pusan.ac.kr [Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Park, Yeong-Min, E-mail: immunpym@pusan.ac.kr [Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of); Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770 (Korea, Republic of)

2011-08-05

Highlights: {yields} Treatment with Rv0462 induces the expression of surface molecules and the production of cytokines in DCs. {yields} Rv0462 induces the activation of MAPKs. {yields} Rv0462-treated DCs enhances the proliferation of CD4{sup +} T cells. -- Abstract: Mycobacterium tuberculosis, the etiological factor of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). In this study, we demonstrated that the gene encoding lipoamide dehydrogenase C (lpdC) from M. tuberculosis, Rv0462, induce maturation and activation of DCs involved in the MAPKs signaling pathway. Moreover, Rv0462-treated DCs activated naive T cells, polarized CD4{sup +} and CD8{sup +} T cells to secrete IFN-{gamma} in syngeneic mixed lymphocyte reactions, which would be expected to contribute to Th1 polarization of the immune response. Our results suggest that Rv0462 can contribute to the innate and adaptive immune responses during tuberculosis infection, and thus modulate the clinical course of tuberculosis.

Mycobacterium tuberculosislpdC, Rv0462, induces dendritic cell maturation and Th1 polarization

International Nuclear Information System (INIS)

Heo, Deok Rim; Shin, Sung Jae; Kim, Woo Sik; Noh, Kyung Tae; Park, Jin Wook; Son, Kwang Hee; Park, Won Sun; Lee, Min-Goo; Kim, Daejin; Shin, Yong Kyoo; Jung, In Duk; Park, Yeong-Min

2011-01-01

Highlights: → Treatment with Rv0462 induces the expression of surface molecules and the production of cytokines in DCs. → Rv0462 induces the activation of MAPKs. → Rv0462-treated DCs enhances the proliferation of CD4 + T cells. -- Abstract: Mycobacterium tuberculosis, the etiological factor of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). In this study, we demonstrated that the gene encoding lipoamide dehydrogenase C (lpdC) from M. tuberculosis, Rv0462, induce maturation and activation of DCs involved in the MAPKs signaling pathway. Moreover, Rv0462-treated DCs activated naive T cells, polarized CD4 + and CD8 + T cells to secrete IFN-γ in syngeneic mixed lymphocyte reactions, which would be expected to contribute to Th1 polarization of the immune response. Our results suggest that Rv0462 can contribute to the innate and adaptive immune responses during tuberculosis infection, and thus modulate the clinical course of tuberculosis.

Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition.

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Chin-Tong Ong

2008-07-01

Full Text Available Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4(+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4(+ T or reporter cells, the presence of Lunatic Fringe in CD4(+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4(+ T cells lacking gamma-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation.

Effect of xanthohumol on Th1/Th2 balance in a breast cancer mouse model.

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Zhang, Wenchao; Pan, Yanlong; Gou, Panhong; Zhou, Cheng; Ma, Lianqing; Liu, Qiming; Du, Yuping; Yang, Jinbo; Wang, Qin

2018-01-01

Xanthohumol (XN), a prenylflavonoid found in the hop plant, Humulus lupulus, exhibits a variety of biological activities. Numerous studies have reported that XN inhibits the growth of many types of cancer cells, but the effects of XN on tumor immunity have not yet been studied. We explored the effect of XN on Th1/Th2 balance and the underlying mechanism based on a BALB/c-4T1 breast cancer mouse model. The results showed that XN significantly slowed down tumor growth and inhibited expression of antitumor proliferation protein Ki-67 as well as breast cancer-specific marker cancer antigen 15-3 (CA15-3). Flow cytometric analysis revealed that XN enhanced the secretion of perforin, granzyme B and increased the ratio of CD8+/CD25+. ELISA analysis of cytokine results demonstrated that XN obviously upregulated Th1 cytokines, while downregulated Th2 cytokines. Th1/Th2 ratio analysis by flow cytometry illustrated that XN regulated the balance drift to Th1 polarization. Western blotting and immunohistochemistry (IHC) results manifested that XN induced expression of T-bet, a Th1-specific transcription factor. Furthermore, we found that XN significantly promoted the phosphorylation of signal transducer and activator of transcription (STAT)4. Our results demonstrated that XN promoted Th1/Th2 balance towards Th1 polarization, and STAT4 may play a positive role in the regulation of Th1/Th2 cytokines by XN.

Design process for applying the nonlocal thermal transport iSNB model to a Polar-Drive ICF simulation

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Cao, Duc; Moses, Gregory; Delettrez, Jacques; Collins, Timothy

2014-10-01

A design process is presented for the nonlocal thermal transport iSNB (implicit Schurtz, Nicolai, and Busquet) model to provide reliable nonlocal thermal transport in polar-drive ICF simulations. Results from the iSNB model are known to be sensitive to changes in the SNB ``mean free path'' formula, and the latter's original form required modification to obtain realistic preheat levels. In the presented design process, SNB mean free paths are first modified until the model can match temperatures from Goncharov's thermal transport model in 1D temperature relaxation simulations. Afterwards the same mean free paths are tested in a 1D polar-drive surrogate simulation to match adiabats from Goncharov's model. After passing the two previous steps, the model can then be run in a full 2D polar-drive simulation. This research is supported by the University of Rochester Laboratory for Laser Energetics.

Preparing for polar-drive ignition on the National Ignition Facility

OpenAIRE

McKenty P.W.; Collins T.J.B.; Marozas J.A.; Kessler T.J.; Zuegel J.D.; Shoup M.J.; Craxton R.S.; Marshall F.J.; Shvydky A.; Skupsky S.; Goncharov V.N.; Radha P.B.; Epstein R.; Sangster T.C.; Meyerhofer D.D.

2013-01-01

The implementation of polar drive (PD) at the National Ignition Facility (NIF) will enable the execution of direct-drive implosions while the facility is configured for x-ray drive. The Laboratory for Laser Energetics (LLE), in collaboration with LLNL, LANL and GA, is implementing PD on the NIF. LLE has designed and participates in the use of PD implosions for diagnostic commissioning on the NIF. LLE has an active experimental campaign to develop PD in both warm and cryogenic target experimen...

n3 PUFAs reduce mouse CD4+ T-cell ex vivo polarization into Th17 cells.

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Monk, Jennifer M; Hou, Tim Y; Turk, Harmony F; McMurray, David N; Chapkin, Robert S

2013-09-01

Little is known about the impact of n3 (ω3) PUFAs on polarization of CD4(+) T cells into effector subsets other than Th1 and Th2. We assessed the effects of dietary fat [corn oil (CO) vs. fish oil (FO)] and fermentable fiber [cellulose (C) vs. pectin (P)] (2 × 2 design) in male C57BL/6 mice fed CO-C, CO-P, FO-C, or FO-P diets for 3 wk on the ex vivo polarization of purified splenic CD4(+) T cells (using magnetic microbeads) into regulatory T cells [Tregs; forkhead box P3 (Foxp3(+)) cells] or Th17 cells [interleukin (IL)-17A(+) and retinoic acid receptor-related orphan receptor (ROR) γτ(+) cells] by flow cytometry. Treg polarization was unaffected by diet; however, FO independently reduced the percentage of both CD4(+) IL-17A(+) (P diets enriched in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or DHA + EPA similarly reduced Th17-cell polarization in comparison to CO by reducing expression of the Th17-cell signature cytokine (IL-17A; P = 0.0015) and transcription factor (RORγτ P = 0.02), whereas Treg polarization was unaffected. Collectively, these data show that n3 PUFAs exert a direct effect on the development of Th17 cells in healthy mice, implicating a novel n3 PUFA-dependent, anti-inflammatory mechanism of action via the suppression of the initial development of this inflammatory T-cell subset.

n3 PUFAs Reduce Mouse CD4+ T-Cell Ex Vivo Polarization into Th17 Cells123

Science.gov (United States)

Monk, Jennifer M.; Hou, Tim Y.; Turk, Harmony F.; McMurray, David N.; Chapkin, Robert S.

2013-01-01

Little is known about the impact of n3 (ω3) PUFAs on polarization of CD4+ T cells into effector subsets other than Th1 and Th2. We assessed the effects of dietary fat [corn oil (CO) vs. fish oil (FO)] and fermentable fiber [cellulose (C) vs. pectin (P)] (2 × 2 design) in male C57BL/6 mice fed CO-C, CO-P, FO-C, or FO-P diets for 3 wk on the ex vivo polarization of purified splenic CD4+ T cells (using magnetic microbeads) into regulatory T cells [Tregs; forkhead box P3 (Foxp3+) cells] or Th17 cells [interleukin (IL)-17A+ and retinoic acid receptor-related orphan receptor (ROR) γτ+ cells] by flow cytometry. Treg polarization was unaffected by diet; however, FO independently reduced the percentage of both CD4+ IL-17A+ (P diets enriched in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or DHA + EPA similarly reduced Th17-cell polarization in comparison to CO by reducing expression of the Th17-cell signature cytokine (IL-17A; P = 0.0015) and transcription factor (RORγτ P = 0.02), whereas Treg polarization was unaffected. Collectively, these data show that n3 PUFAs exert a direct effect on the development of Th17 cells in healthy mice, implicating a novel n3 PUFA–dependent, anti-inflammatory mechanism of action via the suppression of the initial development of this inflammatory T-cell subset. PMID:23864512

Galectin-7 promotes proliferation and Th1/2 cells polarization toward Th1 in activated CD4+ T cells by inhibiting The TGFβ/Smad3 pathway.

Science.gov (United States)

Luo, Zhenlong; Ji, Yudong; Tian, Dean; Zhang, Yong; Chang, Sheng; Yang, Chao; Zhou, Hongmin; Chen, Zhonghua Klaus

2018-06-08

Galectin-7 (Gal-7) has been associated with cell proliferation and apoptosis. It is known that Gal-7 antagonises TGFβ-mediated effects in hepatocytes by interacting with Smad3. Previously, we have demonstrated that Gal-7 is related to CD4+ T cells responses; nevertheless, its effect and functional mechanism on CD4+ T cells responses remain unclear. The murine CD4+ T cells were respectively cultured with Gal-7, anti-CD3/CD28 mAbs, or with anti-CD3/CD28 mAbs & Gal-7. The effects of Gal-7 on proliferation and the phenotypic changes in CD4+ T cells were assessed by flow cytometry. The cytokines from CD4+ T cells were analysed by quantitative real-time PCR. Subcellular localisation and expression of Smad3 were determined by immunofluorescence staining and Western blot, respectively. Gal-7 enhanced the proliferation of activated CD4+ T cells in a dose- and β-galactoside-dependent manner. Additionally, Gal-7 treatment did not change the ratio of Th2 cells in activated CD4+ T cells, while it increased the ratio of Th1 cells. Gal-7 also induced activated CD4+ T cells to produce a higher level of IFN-γ and TNF-α and a lower level of IL-10. Moreover, Gal-7 treatment significantly accelerated nuclear export of Smad3 in activated CD4+ T cells. These results revealed a novel role of Gal-7 in promoting proliferation and Th1/2 cells polarization toward Th1 in activated CD4+ T cells by inhibiting the TGFβ/Smad3 pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression.

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Liu, Hou-Pu; Cao, Anthony T; Feng, Ting; Li, Qingjie; Zhang, Wenbo; Yao, Suxia; Dann, Sara M; Elson, Charles O; Cong, Yingzi

2015-04-01

Differentiated CD4(+) T cells preserve plasticity under various conditions. However, the stability of Th1 cells is unclear, as is whether Th1 cells can convert into Th17 cells and thereby contribute to the generation of IFN-γ(+) IL-17(+) CD4(+) T cells, the number of which correlates with severity of colitis. We investigated whether IFN-γ(+) Th1 cells can convert into Th17 cells under intestinal inflammation and the mechanisms involved. IFN-γ(Thy1.1+) Th1 cells were generated by culturing naïve CD4(+) T cells from IFN-γ(Thy1.1) CBir1 TCR-Tg reporter mice, whose TCR is specific for an immunodominant microbiota antigen, CBir1 flagellin, under Th1 polarizing conditions. IFN-γ(Thy1.1+) Th1 cells induced colitis in Rag(-/-) mice after adoptive transfer and converted into IL-17(+) Th17, but not Foxp3(+) Treg cells in the inflamed intestines. TGF-β and IL-6, but not IL-1β and IL-23, regulated Th1 conversion into Th17 cells. TGF-β induction of transcriptional factor Runx1 is crucial for the conversion, since silencing Runx1 by siRNA inhibited Th1 conversion into Th17 cells. Furthermore, TGF-β enhanced histone H3K9 acetylation but inhibited H3K9 trimethylation of Runx1- and ROR-γt-binding sites on il-17 or rorc gene in Th1 cells. We conclude that Th1 cells convert into Th17 cells under inflammatory conditions in intestines, which is possibly mediated by TGF-β induction of Runx1. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

spv locus aggravates Salmonella infection of zebrafish adult by inducing Th1/Th2 shift to Th2 polarization.

Science.gov (United States)

Wu, Shu-Yan; Wang, Li-Dan; Xu, Guang-Mei; Yang, Si-di; Deng, Qi-Feng; Li, Yuan-Yuan; Huang, Rui

2017-08-01

Salmonella enterica serovar typhimurium (S. typhimurium) are facultative intracellular enteric pathogens causing disease with a broad range of hosts. It was known that Th1-type cytokines such as IFN-γ, IL-12, and TNF-α etc. could induce protective immunity against intracellular pathogens, while Th2-type cytokines such as IL-4, IL-10, and IL-13 etc. are proved to help pathogens survive inside hosts and cause severe infection. One of the critical virulence factor attributes to the pathogenesis of S. typhimurium is Salmonella plasmid virulence genes (spv). Until now, the interaction between spv locus and the predictable generation of Th1 or Th2 immune responses to Salmonella has not been identified. In this study, zebrafish adults were employed to explore the effect of spv locus on Salmonella pathogenesis as well as host adaptive immune responses especially shift of Th1/Th2 balance. The pathological changes of intestines and livers in zebrafish were observed by hematoxylin-eosin (HE) staining and electron microscopy. Levels of the transcription factors of Th1 (Tbx21) and Th2 (GATA3) were measured by real-time quantitative PCR (RT-qPCR). Expression of cytokines were determined by using RT-qPCR and ELISA, respectively. Results showed that spv operon aggravates damage of zebrafish. Furthermore, it demonstrated that spv locus could inhibit the transcription of tbx21 gene and suppress the expression of cytokines IFN-γ, IL-12 and TNF-α. On the contrary, the transcription of gata3 gene could be promoted and the expression of cytokines IL-4, IL-10 and IL-13 were enhanced by spv locus. Taken together, our data revealed that spv locus could aggravate Salmonella infection of zebrafish adult by inducing an imbalance of Th1/Th2 immune response and resulting in a detrimental Th2 bias of host. Copyright © 2017. Published by Elsevier Ltd.

A sea urchin lectin, SUL-1, from the Toxopneustid sea urchin induces DC maturation from human monocyte and drives Th1 polarization in vitro

International Nuclear Information System (INIS)

Takei, Masao; Nakagawa, Hideyuki

2006-01-01

The sea urchin Toxopneustes pileolus belonging to the family Toxopneustidae, they have well-developed globiferous pedicellariae with pharmacologically active substances. We have purified a novel sea urchin lectin-1 (SUL-1) from the large globiferous pedicellariae of T. pileolus. Dendritic cells (DC) are professional APC and play a pivotal role in controlling immune responses. This study investigated whether SUL-1 can drive DC maturation from human immature monocyte-derived DC in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days followed by another 1 day in the presence of SUL-1 or LPS. DC harvested on day 7 were examined using functional assays. The expression levels of CD1a, CD80, CD83, CD86 and HLA-DR as expressed by mean fluorescence intensity (MFI) on DC differentiated from immature DC after culture with 1.0 μg/ml of SUL-1 for 1 day were enhanced and decreased endocytic activity. SUL-1-treated DC also displayed enhanced T cell stimulatory capacity in an MLR, as measured by T cell proliferation. Cell surface expression of CD80, CD83 and CD86 on SUL-1-treated DC was inhibited by anti-DC-SIGN mAb, while anti-DC-SIGN mAb had no influence on allogeneic T cell proliferation by SUL-1-treated DC. DC differentiated with SUL-1 induced the differentiation of naive T cell towards a helper T cell type 1 (Th1) response at DC/T (1:5) cells ratio depending on IL-12 secretion. In CTL assay, the production of IFN-γ and 51 Cr release on SUL-1-treated DC were more augmented than of immature DC or LPS-treated DC. SUL-1-treated DC expressed CCR7 and had a high migration to MIP-3β. Intracellular Ca 2+ mobilization in SUL-1-treated DC was also induced by MIP-3β. These results suggest that SUL-1 bindings to DC-SIGN on surface of immature DC may lead to differentiate DC from immature DC. Moreover, it suggests that SUL-1 may be used on DC-based vaccines for cancer immunotherapy

Polar-Drive Experiments at the National Ignition Facility

Science.gov (United States)

Hohenberger, M.

2014-10-01

To support direct-drive inertial confinement fusion (ICF) experiments at the National Ignition Facility (NIF) in its indirect-drive beam configuration, the polar-drive (PD) concept has been proposed. It requires direct-drive-specific beam smoothing, phase plates, and repointing the NIF beams toward the equator to ensure symmetric target irradiation. First experiments testing the performance of ignition-relevant PD implosions at the NIF have been performed. The goal of these early experiments was to develop a stable, warm implosion platform to investigate laser deposition and laser-plasma instabilities at ignition-relevant plasma conditions, and to develop and validate ignition-relevant models of laser deposition and heat conduction. These experiments utilize the NIF in its current configuration, including beam geometry, phase plates, and beam smoothing. Warm, 2.2-mm-diam plastic shells were imploded with total drive energies ranging from ~ 350 to 750 kJ with peak powers of 60 to 180 TW and peak on-target intensities from 4 ×1014 to 1 . 2 ×1015 W/cm2. Results from these initial experiments are presented, including the level of hot-electron preheat, and implosion symmetry and shell trajectory inferred via self-emission imaging and backlighting. Experiments are simulated with the 2-D hydrodynamics code DRACO including a full 3-D ray trace to model oblique beams, and a model for cross-beam energy transfer (CBET). These simulations indicate that CBET affects the shell symmetry and leads to a loss of energy imparted onto the shell, consistent with the experimental data. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

Interleukin-33 promoting Th1 lymphocyte differentiation dependents on IL-12.

Science.gov (United States)

Komai-Koma, Mousa; Wang, Eryi; Kurowska-Stolarska, Mariola; Li, Dong; McSharry, Charles; Xu, Damo

2016-03-01

The pro-Th2 cytokine IL-33 is now emerging as an important Th1 cytokine-IFN-γ inducer in murine CD4(+) T cells that is essential for protective cell-mediated immunity against viral infection in mice. However, whether IL-33 can promote human Th1 cell differentiation and how IL-33 polarizes Th1 cells is less understood. We assessed the ability of IL-33 to induce Th1 cell differentiation and IFN-γ production in vitro and in vivo. We report here that IL-33 alone had no ability in Th1 cell polarization. However it potentiated IL-12-mediated Th1 cell differentiation and IFN-γ production in TCR-stimulated murine and human CD4(+) T cells in vitro and in vivo. IL-33 promoted Th1 cell development via MyD88 and synergized with IL-12 to enhance St2 and IL-12R expression in CD4(+) T cells. These data therefore provide a novel mechanism for Th1 cell differentiation and optimal induction of a Type 1 response. Thus, IL-33 is capable of inducing IL-12-dependent Th1 cell differentiation in human and mouse CD4(+) T cells. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

Modelo natural de dicotomía TH1-TH2: La enfermedad de Hansen Th1-TH2 balance. Natural model: Hansen'disease

Directory of Open Access Journals (Sweden)

N. L Vaquero

2010-09-01

Full Text Available La enfermedad de Hansen producida por el Mycobacterium leprae, es una enfermedad infecciosa cuyo amplio espectro clínico e inmunopatológico se correlaciona con los diferentes patrones de respuesta Th1/Th2. La activación preferencial de esas subpoblaciones de linfocitos T CD4 juega un rol importante en su patogenia y constituye un modelo natural de esa dicotomía de la respuesta inmune. Ambas formas polares de la lepra presentan un perfil definido de secreción de citoquinas: Th1 (IL2 e IFN? en el polo tuberculoide y Th2 (IL4, IL5, IL10 en el polo lepromatoso. En el primer caso, la respuesta celular adecuada estimula la activación macrofágica y lleva a la destrucción del bacilo. Las lesiones son escasas y limitadas a la piel y nervios periféricos. En el segundo en cambio, la respuesta celular es casi nula y los bacilos se multiplican descontroladamente dentro de los macrófagos, llevando a la diseminación de las lesiones y afectación de otros órganos. La inmunidad humoral está exacerbada y hay un alto nivel de anticuerpos que no pueden eliminar el germen intracelular. Los factores que determinan la diferenciación hacia una respuesta Th1 ó Th2 no se han esclarecido totalmente. Se han postulado varias hipótesis que hacen referencia a factores genéticos, prevalencia de citoquinas en el microambiente celular, disfunción macrofágica; alteración en los receptores Toll de la inmunidad innata, en la expresión de moléculas coestimulatorias, etc En los últimos años se han descubierto nuevas subpoblaciones de linfocitos, (CD4+ CD25+, Tr1, Th3 y Th17 que estarían implicadas en la desregulación de estas respuestas inmunes.Hansen' disease, caused by Mycobacterium leprae, is an infectious illness whose wide clinical and immunopathologic spectrum correl with different Th1/Th2 responses patterns. The prefferencial activation of the CD4 T cells subset play an important rol in it's pathogenia and provides a natural model of that balance

Intestinal Irradiation and Fibrosis in a Th1-Deficient Environment

International Nuclear Information System (INIS)

Linard, Christine; Billiard, Fabienne; Benderitter, Marc

2012-01-01

Purpose: Changes in the Th1/Th2 immune balance may play a role in increasing the incidence of radiation-induced toxicity. This study evaluates the consequences of Th1 deficiency on intestinal response (fibrosis and T cell trafficking) to abdominal irradiation and examines in mucosa and mesenteric lymph nodes (MLN) the differential involvement of the two Th1 pathways, T-bet/STAT1 and IL-12/STAT4, in controlling this balance in mice. Methods and Materials: Using T-bet-deficient mice (T-bet −/− ), we evaluated the mRNA and protein expression of the Th1 pathways (IFN-γ, T-bet/STAT1, and IL-12/STAT4) and the CD4 + and CD8 + populations in ileal mucosa and MLN during the first 3 months after 10 Gy abdominal irradiation. Results: The T-bet-deficient mice showed an increased fibrotic response to radiation, characterized by higher TGF-β1, col3a1 expression, and collagen deposition in mucosa compared with wild-type mice. This response was associated with drastically lower expression of IFN-γ, the hallmark Th1 cytokine. Analysis of the Th1 expression pathways, T-bet/STAT1 and IL-12/STAT4, showed their equal involvement in the failure of Th1 polarization. A minimal IFN-γ level depended on the IL-23-p19/STAT4 level. In addition, the radiation-induced deficiency in the priming of Th1 by IFN-γ was related to the defective homing capacity of CD8 + cells in the mucosa. Conclusion: Irradiation induces Th2 polarization, and the Th2 immune response may play a role in potentiating irradiation-induced intestinal collagen deposition.

Intestinal Irradiation and Fibrosis in a Th1-Deficient Environment

Energy Technology Data Exchange (ETDEWEB)

Linard, Christine, E-mail: christine.linard@irsn.fr [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France); Billiard, Fabienne; Benderitter, Marc [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France)

2012-09-01

Purpose: Changes in the Th1/Th2 immune balance may play a role in increasing the incidence of radiation-induced toxicity. This study evaluates the consequences of Th1 deficiency on intestinal response (fibrosis and T cell trafficking) to abdominal irradiation and examines in mucosa and mesenteric lymph nodes (MLN) the differential involvement of the two Th1 pathways, T-bet/STAT1 and IL-12/STAT4, in controlling this balance in mice. Methods and Materials: Using T-bet-deficient mice (T-bet{sup -/-}), we evaluated the mRNA and protein expression of the Th1 pathways (IFN-{gamma}, T-bet/STAT1, and IL-12/STAT4) and the CD4{sup +} and CD8{sup +} populations in ileal mucosa and MLN during the first 3 months after 10 Gy abdominal irradiation. Results: The T-bet-deficient mice showed an increased fibrotic response to radiation, characterized by higher TGF-{beta}1, col3a1 expression, and collagen deposition in mucosa compared with wild-type mice. This response was associated with drastically lower expression of IFN-{gamma}, the hallmark Th1 cytokine. Analysis of the Th1 expression pathways, T-bet/STAT1 and IL-12/STAT4, showed their equal involvement in the failure of Th1 polarization. A minimal IFN-{gamma} level depended on the IL-23-p19/STAT4 level. In addition, the radiation-induced deficiency in the priming of Th1 by IFN-{gamma} was related to the defective homing capacity of CD8{sup +} cells in the mucosa. Conclusion: Irradiation induces Th2 polarization, and the Th2 immune response may play a role in potentiating irradiation-induced intestinal collagen deposition.

Neuropeptide Y induces potent migration of human immature dendritic cells and promotes a Th2 polarization.

Science.gov (United States)

Buttari, Brigitta; Profumo, Elisabetta; Domenici, Giacomo; Tagliani, Angela; Ippoliti, Flora; Bonini, Sergio; Businaro, Rita; Elenkov, Ilia; Riganò, Rachele

2014-07-01

Neuropeptide Y (NPY), a major autonomic nervous system and stress mediator, is emerging as an important regulator of inflammation, implicated in autoimmunity, asthma, atherosclerosis, and cancer. Yet the role of NPY in regulating phenotype and functions of dendritic cells (DCs), the professional antigen-presenting cells, remains undefined. Here we investigated whether NPY could induce DCs to migrate, mature, and polarize naive T lymphocytes. We found that NPY induced a dose-dependent migration of human monocyte-derived immature DCs through the engagement of NPY Y1 receptor and the activation of ERK and p38 mitogen-activated protein kinases. NPY promoted DC adhesion to endothelial cells and transendothelial migration. It failed to induce phenotypic DC maturation, whereas it conferred a T helper 2 (Th2) polarizing profile to DCs through the up-regulation of interleukin (IL)-6 and IL-10 production. Thus, during an immune/inflammatory response NPY may exert proinflammatory effects through the recruitment of immature DCs, but it may exert antiinflammatory effects by promoting a Th2 polarization. Locally, at inflammatory sites, cell recruitment could be amplified in conditions of intense acute, chronic, or cold stress. Thus, altered or amplified signaling through the NPY-NPY-Y1 receptor-DC axis may have implications for the development of inflammatory conditions.-Buttari, B., Profumo, E., Domenici, G., Tagliani, A., Ippoliti, F., Bonini, S., Businaro, R., Elenkov, I., Riganò, R. Neuropeptide Y induces potent migration of human immature dendritic cells and promotes a Th2 polarization. © FASEB.

Effect of driving voltage polarity on dynamic response characteristics of electrowetting liquid lens

Science.gov (United States)

Na, Xie; Ning, Zhang; Rong-Qing, Xu

2018-05-01

A test device is developed for studying the dynamic process of an electrowetting liquid lens. By analyzing the light signals through the liquid lens, the dynamical properties of the lens are investigated. In our experiment, three types of pulse, i.e., sine, bipolar pulse, and single pulse signals, are employed to drive the liquid lens, and the dynamic characteristics of the lens are subsequently analyzed. The results show that the positive and negative polarities of the driving voltage can cause a significant difference in the response of the liquid lens; meanwhile, the lens’s response to the negative polarity of the driving voltage is clearer. We use the theory of charge restraint to explain this phenomenon, and it is concluded that the negative ions are more easily restrained by a dielectric layer. This work gives direct guidance for practical applications based on an electrowetting liquid lens.

Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway.

Science.gov (United States)

Mariotti, Jacopo; Foley, Jason; Ryan, Kaitlyn; Buxhoeveden, Nicole; Kapoor, Veena; Amarnath, Shoba; Fowler, Daniel H

2008-12-01

Graft rejection has been defined as the mirror image of graft-versus-host disease, which is biologically characterized primarily as a Th1-type process. As such, we reasoned that graft rejection would represent a Th1 response amenable to Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated rejection of fully MHC-disparate murine bone marrow allografts more effectively than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not differentiate into Th1-type cells in vivo and failed to mediate rejection. We next hypothesized that donor Th2 cell allograft augmentation would prevent rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2 cell therapy, host-anti-donor allospecific T cells acquired Th2 polarity, persisted posttransplantation, and did not mediate rejection. Abrogation of rejection required donor Th2 cell IL-4 secretion and host T-cell STAT6 signaling. In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1-type process that can be abrogated by donor Th2 cell therapy that promotes engraftment through a novel mechanism whereby cytokine polarization is transferred to host T cells.

OMEGA polar-drive target designs

International Nuclear Information System (INIS)

Radha, P. B.; Marozas, J. A.; Marshall, F. J.; Shvydky, A.; Collins, T. J. B.; Goncharov, V. N.; McKenty, P. W.; Sangster, T. C.; Skupsky, S.; McCrory, R. L.; Meyerhofer, D. D.

2012-01-01

Low-adiabat polar-drive (PD) [Skupsky et al., Phys. Plasmas 11, 2763 (2004)] implosion designs for the OMEGA [Boehly et al., Opt. Commun. 133, 495 (1997)] laser are described. These designs for cryogenic deuterium–tritium and warm plastic shells use a temporal laser pulse shape with three pickets followed by a main pulse [Goncharov et al., Phys. Rev. Lett. 104, 165001 (2010)]. The designs are at two different on-target laser intensities, with different in-flight aspect ratios (IFARs). These designs permit studies of implosion energetics and target performance closer to ignition-relevant intensities (∼7 × 10 14 W/cm 2 at the quarter-critical surface, where nonlocal heat conduction and laser–plasma interactions can play an important role) but at lower values of IFAR ∼ 22 or at lower intensity (∼3 × 10 14 W/cm 2 ) but at a higher IFAR (IFAR ∼ 32, where shell instability can play an important role). PD geometry requires repointing of laser beams to improve shell symmetry. The higher-intensity designs optimize target performance by repointing beams to a lesser extent, compensating for the reduced equatorial drive by increasing the energies of the repointed beams. They also use custom beam profiles that improve equatorial illumination at the expense of irradiation at higher latitudes. These latter designs will be studied when new phase plates for the OMEGA Laser System, corresponding to the custom beam profiles, are obtained.

Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

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Federica Raggi

2017-09-01

Full Text Available Macrophages (Mf are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1 and alternatively activated (anti-inflammatory M2 subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment.

Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

Science.gov (United States)

Raggi, Federica; Pelassa, Simone; Pierobon, Daniele; Penco, Federica; Gattorno, Marco; Novelli, Francesco; Eva, Alessandra; Varesio, Luigi; Giovarelli, Mirella; Bosco, Maria Carla

2017-01-01

Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM)-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment. PMID:28936211

Polar-direct-drive experiments on the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Hohenberger, M.; Radha, P. B.; Myatt, J. F.; Marozas, J. A.; Marshall, F. J.; Michel, D. T.; Regan, S. P.; Seka, W.; Shvydky, A.; Sangster, T. C.; Betti, R.; Boehly, T. R.; Bonino, M. J.; Collins, T. J. B.; Craxton, R. S.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Fiksel, G.; Froula, D. H. [Laboratory for Laser Energetics, University of Rochester, Rochester, New York 14623-1299 (United States); and others

2015-05-15

To support direct-drive inertial confinement fusion experiments at the National Ignition Facility (NIF) [G. H. Miller, E. I. Moses, and C. R. Wuest, Opt. Eng. 43, 2841 (2004)] in its indirect-drive beam configuration, the polar-direct-drive (PDD) concept [S. Skupsky et al., Phys. Plasmas 11, 2763 (2004)] has been proposed. Ignition in PDD geometry requires direct-drive–specific beam smoothing, phase plates, and repointing the NIF beams toward the equator to ensure symmetric target irradiation. First experiments to study the energetics and preheat in PDD implosions at the NIF have been performed. These experiments utilize the NIF in its current configuration, including beam geometry, phase plates, and beam smoothing. Room-temperature, 2.2-mm-diam plastic shells filled with D{sub 2} gas were imploded with total drive energies ranging from ∼500 to 750 kJ with peak powers of 120 to 180 TW and peak on-target irradiances at the initial target radius from 8 × 10{sup 14} to 1.2 × 10{sup 15 }W/cm{sup 2}. Results from these initial experiments are presented, including measurements of shell trajectory, implosion symmetry, and the level of hot-electron preheat in plastic and Si ablators. Experiments are simulated with the 2-D hydrodynamics code DRACO including a full 3-D ray-trace to model oblique beams, and models for nonlocal electron transport and cross-beam energy transport (CBET). These simulations indicate that CBET affects the shell symmetry and leads to a loss of energy imparted onto the shell, consistent with the experimental data.

The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.

Science.gov (United States)

Takahashi, Noriyuki; Saitoh, Takayuki; Gotoh, Nanami; Nitta, Yasuhiro; Alkebsi, Lobna; Kasamatsu, Tetsuhiro; Minato, Yusuke; Yokohama, Akihiko; Tsukamoto, Norifumi; Handa, Hiroshi; Murakami, Hirokazu

2017-05-16

T-helper cell type 1 (Th1) polarization in chronic immune thrombocytopenia (cITP) has been reported at the protein and mRNA levels. We evaluated the impact of Th1/Th2 cytokine and cytokine receptor functional polymorphisms on both susceptibility to, and severity of, cITP. We analysed IFN-γ + 874 T/A, IFN-γR -611G/A, IL-4 -590C/T, and IL-4Rα Q576R polymorphisms in 126 cITP patients (male/female: 34/92; median age: 47.7 years) and 202 healthy control donors. Genotyping was determined by PCR and direct sequencing. The Th1/Th2 ratio was detected in peripheral blood mononuclear cells via flow cytometry. cITP patients had a higher frequency of the IL-4Rα 576 non-QQ genotype compared to healthy subjects (P = 0.04). cITP patients with the IFN-γ +874 non-AA genotype (high expression type) showed more severe thrombocytopenia than those with the AA genotype (P Th1/Th2 ratio than control patients (P Th1/Th2 ratio (P Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.

Designing symmetric polar direct drive implosions on the Omega laser facility

Energy Technology Data Exchange (ETDEWEB)

Krasheninnikova, Natalia S.; Cobble, James A.; Murphy, Thomas J.; Tregillis, Ian L.; Bradley, Paul A.; Hakel, Peter; Hsu, Scott C.; Kyrala, George A.; Obrey, Kimberly A.; Schmitt, Mark J.; Baumgaertel, Jessica A.; Batha, Steven H. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

2014-04-15

Achieving symmetric capsule implosions with Polar Direct Drive [S. Skupsky et al., Phys. Plasmas 11, 2763 (2004); R. S. Craxton et al., Phys. Plasmas 12, 056304 (2005); F. J. Marshall et al., J. Phys. IV France 133, 153–157 (2006)] has been explored during recent Defect Induced Mix Experiment campaign on the Omega facility at the Laboratory for Laser Energetics. To minimize the implosion asymmetry due to laser drive, optimized laser cone powers, as well as improved beam pointings, were designed using 3D radiation-hydrodynamics code HYDRA [M. M. Marinak et al., Phys. Plasmas 3, 2070 (1996)]. Experimental back-lit radiographic and self-emission images revealed improved polar symmetry and increased neutron yield which were in good agreement with 2D HYDRA simulations. In particular, by reducing the energy in Omega's 21.4° polar rings by 16.75%, while increasing the energy in the 58.9° equatorial rings by 8.25% in such a way as to keep the overall energy to the target at 16 kJ, the second Legendre mode (P{sub 2}) was reduced by a factor of 2, to less than 4% at bang time. At the same time the neutron yield increased by 62%. The polar symmetry was also improved relative to nominal DIME settings by a more radical repointing of OMEGA's 42.0° and 58.9° degree beams, to compensate for oblique incidence and reduced absorption at the equator, resulting in virtually no P{sub 2} around bang time and 33% more yield.

Dendritic Cell-Induced Th1 and Th17 Cell Differentiation for Cancer Therapy

Directory of Open Access Journals (Sweden)

Julia Terhune

2013-11-01

Full Text Available The success of cellular immunotherapies against cancer requires the generation of activated CD4+ and CD8+ T-cells. The type of T-cell response generated (e.g., Th1 or Th2 will determine the efficacy of the therapy, and it is generally assumed that a type-1 response is needed for optimal cancer treatment. IL-17 producing T-cells (Th17/Tc17 play an important role in autoimmune diseases, but their function in cancer is more controversial. While some studies have shown a pro-cancerous role for IL-17, other studies have shown an anti-tumor function. The induction of polarized T-cell responses can be regulated by dendritic cells (DCs. DCs are key regulators of the immune system with the ability to affect both innate and adaptive immune responses. These properties have led many researchers to study the use of ex vivo manipulated DCs for the treatment of various diseases, such as cancer and autoimmune diseases. While Th1/Tc1 cells are traditionally used for their potent anti-tumor responses, mounting evidence suggests Th17/Tc17 cells should be utilized by themselves or for the induction of optimal Th1 responses. It is therefore important to understand the factors involved in the induction of both type-1 and type-17 T-cell responses by DCs.

Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3.

Directory of Open Access Journals (Sweden)

Arundhoti Das

Full Text Available Naïve CD4 T (NCD4T cells post-activation undergo programming for inducible production of cytokines leading to generation of memory cells with various functions. Based on cytokine based polarization of NCD4T cells in vitro, programming for either 'Th1' (interferon-gamma [IFNg] or 'Th2' (interleukin [IL]-4/5/13 cytokines is thought to occur via mutually exclusive expression and functioning of T-bet or GATA-3 transcription factors (TFs. However, we show that a high proportion of mouse and human memory-phenotype CD4 T (MCD4T cells generated in vivo which expressed either Th1 or Th2 cytokines commonly co-expressed T-bet and GATA-3. While T-bet levels did not differ between IFNg-expressing and IL-4/5/13-expressing MCD4T cells, GATA-3 levels were higher in the latter. These observations were also confirmed in MCD4T cells from FVB/NJ or aged C57BL/6 or IFNg-deficient mice. While MCD4T cells from these strains showed greater Th2 commitment than those from young C57BL/6 mice, pattern of co-expression of TF was similar. Effector T cells generated in vivo following immunization also showed TF co-expression in Th1 or Th2 cytokine producing cells. We speculated that the difference in TF expression pattern of MCD4T cells generated in vivo and those generated in cytokine polarized cultures in vitro could be due to relative absence of polarizing conditions during activation in vivo. We tested this by NCD4T cell activation in non-polarizing conditions in vitro. Anti-CD3 and anti-CD28-mediated priming of polyclonal NCD4T cells in vitro without polarizing milieu generated cells that expressed either IFNg or IL-4/5/13 but not both, yet both IFNg- and IL-4/5/13-expressing cells showed upregulation of both TFs. We also tested monoclonal T cell populations activated in non-polarizing conditions. TCR-transgenic NCD4T cells primed in vitro by cognate peptide in non-polarizing conditions which expressed either IFNg or IL-4/5/13 also showed a high proportion of cells co

Introduction: The 6th special issue of Mars Polar Science

Science.gov (United States)

Sori, Michael M.; Brown, Adrian J.

2018-07-01

Polar science at Mars has the ability to elucidate outstanding problems in the planet's history. The long-lived, kilometers-thick deposits at both poles hold a climate record that is still being steadily deciphered (e.g., Becerra et al., 2017), seasonal volatiles are important drivers of geomorphological change (e.g., Pilorget and Forget, 2015), and there is a growing recognition that water ice at lower latitudes is an important piece of the story in understanding polar processes (e.g., Bramson et al., 2015). Additionally, the icy volatiles trapped in the mid-latitudes will be an important resource for future human explorers (e.g., Viola et al., 2015). One task of this generation of Martian polar explorers is to understand the evolution of water as it cycles through the polar and mid-latitudes on geologic timescales in anticipation of its eventual utilization by the next generation of human and robotic explorers. To address these and other topics, the 6th International Mars Polar Science Conference was held in September 2016 in Reykjavik, Iceland (Smith et al., 2018). This special issue represents 16 papers presented at that conference.

Pulsed high-dose dexamethasone modulates Th1-/Th2-chemokine imbalance in immune thrombocytopenia.

Science.gov (United States)

Liu, Zongtang; Wang, Meiying; Zhou, Shufen; Ma, Ji; Shi, Yan; Peng, Jun; Hou, Ming; Guo, Chengshan

2016-10-24

Chemokines and chemokine receptors play important roles in autoimmune diseases; however, their role in immune thrombocytopenia (ITP) is unclear. High-dose dexamethasone (HD-DXM) may become a first-line therapy for adult patients with ITP, but the effect of HD-DXM on chemokines in ITP patients is unknown. Our aim was to investigate the mechanism of pulsed HD-DXM for management of ITP, specifically regarding the chemokine pathways. Th1-/Th2-associated chemokine and chemokine receptor profiles in ITP patients before and after pulsed HD-DXM was studied. Plasma levels of CCL5 and CXCL11 (Th1-associated) and of CCL11 (Th2-associated) were determined by ELISA. Gene expression of these three chemokines and their corresponding receptors CCR5, CXCR3, and CCR3, in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR. Thirty-three of the thirty-eight ITP patients responded effectively to HD-DXM (oral, 40 mg/day, 4 days). In ITP patients, plasma CXCL11 levels increased, while CCL11 and CCL5 decreased compared to controls (P Th1-/Th2-associated chemokines and chemokine receptors may play important roles in the pathogenesis of ITP. Importantly, regulating Th1 polarization by pulsed HD-DXM may represent a novel approach for immunoregulation in ITP.

Spontaneous dressed-state polarization in the strong driving regime of cavity QED.

Science.gov (United States)

Armen, Michael A; Miller, Anthony E; Mabuchi, Hideo

2009-10-23

We utilize high-bandwidth phase-quadrature homodyne measurement of the light transmitted through a Fabry-Perot cavity, driven strongly and on resonance, to detect excess phase noise induced by a single intracavity atom. We analyze the correlation properties and driving-strength dependence of the atom-induced phase noise to establish that it corresponds to the long-predicted phenomenon of spontaneous dressed-state polarization. Our experiment thus provides a demonstration of cavity quantum electrodynamics in the strong-driving regime in which one atom interacts strongly with a many-photon cavity field to produce novel quantum stochastic behavior.

Regnase-1 and Roquin Nonredundantly Regulate Th1 Differentiation Causing Cardiac Inflammation and Fibrosis.

Science.gov (United States)

Cui, Xiaotong; Mino, Takashi; Yoshinaga, Masanori; Nakatsuka, Yoshinari; Hia, Fabian; Yamasoba, Daichi; Tsujimura, Tohru; Tomonaga, Keizo; Suzuki, Yutaka; Uehata, Takuya; Takeuchi, Osamu

2017-12-15

Regnase-1 and Roquin are RNA binding proteins that are essential for degradation of inflammatory mRNAs and maintenance of immune homeostasis. Although deficiency of either of the proteins leads to enhanced T cell activation, their functional relationship in T cells has yet to be clarified because of lethality upon mutation of both Regnase-1 and Roquin. By using a Regnase-1 conditional allele, we show that mutations of both Regnase-1 and Roquin in T cells leads to massive lymphocyte activation. In contrast, mutation of either Regnase-1 or Roquin affected T cell activation to a lesser extent than the double mutation, indicating that Regnase-1 and Roquin function nonredundantly in T cells. Interestingly, Regnase-1 and Roquin double-mutant mice suffered from severe inflammation and early formation of fibrosis, especially in the heart, along with the increased expression of Ifng , but not Il4 or Il17a Consistently, mutation of both Regnase-1 and Roquin leads to a huge increase in the Th1, but not the Th2 or Th17, population in spleens compared with T cells with a single Regnase-1 or Roquin deficiency. Regnase-1 and Roquin are capable of repressing the expression of a group of mRNAs encoding factors involved in Th1 differentiation, such as Furin and Il12rb1 , via their 3' untranslated regions. Moreover, Regnase-1 is capable of repressing Roquin mRNA. This cross-regulation may contribute to the synergistic control of T cell activation/polarization. Collectively, our results demonstrate that Regnase-1 and Roquin maintain T cell immune homeostasis and regulate Th1 polarization synergistically. Copyright © 2017 by The American Association of Immunologists, Inc.

Regulatory Effect of Catalpol on Th1/Th2 cells in Mice with Bone Loss Induced by Estrogen Deficiency.

Science.gov (United States)

Lai, Nannan; Zhang, Jianhai; Ma, Xingyan; Wang, Bin; Miao, Xiuming; Wang, Zhaoxia; Guo, Yuqi; Wang, Li; Yao, Chengfang; Li, Xia; Jiang, Guosheng

2015-12-01

Estradiol (E2 ) deficiency can cause bone loss and the skew of Th1/Th2 cells. However, the correlation between the Th1/Th2 cells and the bone loss induced by estrogen deficiency remains unclear. Our aim was to investigate the role of Th1/Th2 in bone loss induced by estrogen deficiency and elucidated the therapeutical effect of catalpol in this condition. Young, sham-operated (Sham), ovariectomized (Ovx), and naturally aged mice, treated with catalpol at different doses or control vehicle, were used in this study as indicated in each experiment. ELISA assay, dual-energy X-ray absorptiometry, and flow cytometry were used to analyze E2 , C-terminal telopeptides of type I collagen (CTx-I), bone mineral density (BMD), and Th1/Th2 subsets, respectively. The mRNA and protein expressions of specific transcription factors for Th1/Th2 cells (T-bet and GATA-3) were analyzed using real-time quantitative PCR and Western blot, respectively. Bone mineral density and E2 levels positively correlated with the proportion of Th2 subset while negatively correlated with that of Th1 subset and the ratio of Th1/Th2. Catalpol alleviated bone loss effectively by regulating Th1/Th2 polarization. Catalpol promoted the expression of Th2-specific transcription factors while inhibited that associated with Th1. Th1/Th2 skew is involved in bone loss induced by estrogen deficiency. Catalpol alleviates bone loss effectively by regulating Th1/Th2 paradigm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Schistosoma japonicum chimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens

Directory of Open Access Journals (Sweden)

Xue Xiangyang

2009-05-01

Full Text Available Abstract Background Schitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4 via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice. Methods The immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3+CD8-IFN-γ+ cells and CD3+CD8-IL-4+ cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge. Results Immunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced

Obesity Drives Th17 Cell Differentiation by Inducing the Lipid Metabolic Kinase, ACC1.

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Endo, Yusuke; Asou, Hikari K; Matsugae, Nao; Hirahara, Kiyoshi; Shinoda, Kenta; Tumes, Damon J; Tokuyama, Hirotake; Yokote, Koutaro; Nakayama, Toshinori

2015-08-11

Chronic inflammation due to obesity contributes to the development of metabolic diseases, autoimmune diseases, and cancer. Reciprocal interactions between metabolic systems and immune cells have pivotal roles in the pathogenesis of obesity-associated diseases, although the mechanisms regulating obesity-associated inflammatory diseases are still unclear. In the present study, we performed transcriptional profiling of memory phenotype CD4 T cells in high-fat-fed mice and identified acetyl-CoA carboxylase 1 (ACC1, the gene product of Acaca) as an essential regulator of Th17 cell differentiation in vitro and of the pathogenicity of Th17 cells in vivo. ACC1 modulates the DNA binding of RORγt to target genes in differentiating Th17 cells. In addition, we found a strong correlation between IL-17A-producing CD45RO(+)CD4 T cells and the expression of ACACA in obese subjects. Thus, ACC1 confers the appropriate function of RORγt through fatty acid synthesis and regulates the obesity-related pathology of Th17 cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Opportunity's Surroundings on Sol 1798 (Polar)

Science.gov (United States)

2009-01-01

NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this 180-degree view of the rover's surroundings during the 1,798th Martian day, or sol, of Opportunity's surface mission (Feb. 13, 2009). North is on top. This view is presented as a polar projection with geometric seam correction. The rover had driven 111 meters (364 feet) southward on the preceding sol. Tracks from that drive recede northward in this view. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

Opportunity's Surroundings on Sol 1818 (Polar)

Science.gov (United States)

2009-01-01

NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings during the 1,818th Martian day, or sol, of Opportunity's surface mission (March 5, 2009). South is at the center; north at both ends. This view is presented as a polar projection with geometric seam correction. North is at the top. The rover had driven 80.3 meters (263 feet) southward earlier on that sol. Tracks from the drive recede northward in this view. The terrain in this portion of Mars' Meridiani Planum region includes dark-toned sand ripples and lighter-toned bedrock.

Relationships between Th1 or Th2 iNKT cell activity and structures of CD1d-antigen complexes: meta-analysis of CD1d-glycolipids dynamics simulations.

Directory of Open Access Journals (Sweden)

Xavier Laurent

2014-11-01

Full Text Available A number of potentially bioactive molecules can be found in nature. In particular, marine organisms are a valuable source of bioactive compounds. The activity of an α-galactosylceramide was first discovered in 1993 via screening of a Japanese marine sponge (Agelas mauritanius. Very rapidly, a synthetic glycololipid analogue of this natural molecule was discovered, called KRN7000. Associated with the CD1d protein, this α-galactosylceramide 1 (KRN7000 interacts with the T-cell antigen receptor to form a ternary complex that yields T helper (Th 1 and Th2 responses with opposing effects. In our work, we carried out molecular dynamics simulations (11.5 µs in total involving eight different ligands (conducted in triplicate in an effort to find out correlation at the molecular level, if any, between chemical modulation of 1 and the orientation of the known biological response, Th1 or Th2. Comparative investigations of human versus mouse and Th1 versus Th2 data have been carried out. A large set of analysis tools was employed including free energy landscapes. One major result is the identification of a specific conformational state of the sugar polar head, which could be correlated, in the present study, to the biological Th2 biased response. These theoretical tools provide a structural basis for predicting the very different dynamical behaviors of α-glycosphingolipids in CD1d and might aid in the future design of new analogues of 1.

Total glucosides of peony attenuates 2,4,6-trinitrobenzene sulfonic acid/ethanol-induced colitis in rats through adjustment of TH1/TH2 cytokines polarization.

Science.gov (United States)

Zhang, Yabing; Zhou, Rui; Zhou, Feng; Cheng, Hong; Xia, Bing

2014-01-01

The present study is to investigate effects of total glucosides of peony (TGP) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol-induced colitis in rats and to explore potential clinical use of TGP for treatment of inflammatory bowel disease. Sixty Sprague-Dawley rats were randomly grouped into normal controls, model controls, sulfasalazine (SASP) controls (100 mg/kg/day), and low, medium, and high-dose TGP groups (25, 50, and 100 mg/kg/day, respectively). 24 h following colonic instillation of TNBS, TGP, and SASP were given by gastric gavage three times a day for 7 days. Disease activity index (DAI), colon macroscopic damage index (CMDI), histopathological score (HPS), and myeloperoxidase (MPO) activity were evaluated. Levels of serum TNF-α, IL-1β, and IL-10 were measured by ELISA, and expression of TNF-α, IL-1β, and IL-10 mRNA and protein in colonic tissues was detected by RT-PCR and western blot, respectively. Compared with rats in the model controls, TGP (50 or 100 mg/kg/day)-treated rats with TNBS/ethanol-induced colitis showed significant improvements of DAI, CMDI, HPS, and MPO activity. Moreover, administration of TGP (50 or 100 mg/kg/day) decreased the up-regulated levels of serum TNF-α and IL-1β, and expression of TNF-α and IL-1β mRNA and protein in colonic tissues, and increased the serum IL-10 and colonic IL-10 mRNA and protein level. And there was no significant difference compared with administration of SASP (P > 0.05). TGP attenuates TNBS/ethanol-induced colitis in rats and its efficacy is similar to SASP, the potential mechanism might be related to the adjustment of Th1/Th2 cytokines polarization by decreasing pro-inflammatory cytokine TNF-α and IL-1β, and increasing anti-inflammatory cytokine IL-10.

Impaired-driving prevalence among US high school students: associations with substance use and risky driving behaviors.

Science.gov (United States)

Li, Kaigang; Simons-Morton, Bruce G; Hingson, Ralph

2013-11-01

We examined the prevalence of impaired driving among US high school students and associations with substance use and risky driving behavior. We assessed driving while alcohol or drug impaired (DWI) and riding with alcohol- or drug-impaired drivers (RWI) in a nationally representative sample of 11th-grade US high school students (n = 2431). We examined associations with drinking and binge drinking, illicit drug use, risky driving, and demographic factors using multivariate sequential logistic regression analysis. Thirteen percent of 11th-grade students reported DWI at least 1 of the past 30 days, and 24% reported RWI at least once in the past year. Risky driving was positively associated with DWI (odds ratio [OR] = 1.25; P phone calls (OR = 3.2) while driving. Our findings suggest the need for comprehensive approaches to the prevention of DWI, RWI, and other risky driving behavior.

Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

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Lalor, Stephen J.; Leech, John M.; O’Keeffe, Kate M.; Mac Aogáin, Micheál; O’Halloran, Dara P.; Lacey, Keenan A.; Tavakol, Mehri; Hearnden, Claire H.; Fitzgerald-Hughes, Deirdre; Humphreys, Hilary; Fennell, Jérôme P.; van Wamel, Willem J.; Foster, Timothy J.; Geoghegan, Joan A.; Lavelle, Ed C.; Rogers, Thomas R.; McLoughlin, Rachel M.

2015-01-01

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID:26539822

Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

LENUS (Irish Health Repository)

Brown, Aisling F

2015-01-01

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes

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Defrance, Matthieu; Vu Manh, Thien-Phong; Azouz, Abdulkader; Detavernier, Aurélie; Hoyois, Alice; Das, Jishnu; Bizet, Martin; Pollet, Emeline; Tabbuso, Tressy; Calonne, Emilie; van Gisbergen, Klaas; Dalod, Marc; Fuks, François; Goriely, Stanislas

2018-01-01

Cytotoxic CD4 (CD4CTX) T cells are emerging as an important component of antiviral and antitumor immunity, but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant proportion of CD4 T cells displays cytotoxic functions. We observed that the transcriptional program of these cells was enriched in CD8 T cell lineage genes despite the absence of ThPOK downregulation. We further show that establishment of CD4CTX-specific transcriptional and epigenetic programs occurred in a stepwise fashion along the Th1-differentiation pathway. In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK. This work elucidates the molecular program of human CD4CTX T cells and identifies potential targets for immunotherapy against viral infections and cancer. PMID:29488879

Bordetella pertussis commits human dendritic cells to promote a Th1/Th17 response through the activity of adenylate cyclase toxin and MAPK-pathways.

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Giorgio Fedele

Full Text Available The complex pathology of B. pertussis infection is due to multiple virulence factors having disparate effects on different cell types. We focused our investigation on the ability of B. pertussis to modulate host immunity, in particular on the role played by adenylate cyclase toxin (CyaA, an important virulence factor of B. pertussis. As a tool, we used human monocyte derived dendritic cells (MDDC, an ex vivo model useful for the evaluation of the regulatory potential of DC on T cell immune responses. The work compared MDDC functions after encounter with wild-type B. pertussis (BpWT or a mutant lacking CyaA (BpCyaA-, or the BpCyaA- strain supplemented with either the fully functional CyaA or a derivative, CyaA*, lacking adenylate cyclase activity. As a first step, MDDC maturation, cytokine production, and modulation of T helper cell polarization were evaluated. As a second step, engagement of Toll-like receptors (TLR 2 and TLR4 by B. pertussis and the signaling events connected to this were analyzed. These approaches allowed us to demonstrate that CyaA expressed by B. pertussis strongly interferes with DC functions, by reducing the expression of phenotypic markers and immunomodulatory cytokines, and blocking IL-12p70 production. B. pertussis-treated MDDC promoted a mixed Th1/Th17 polarization, and the activity of CyaA altered the Th1/Th17 balance, enhancing Th17 and limiting Th1 expansion. We also demonstrated that Th1 effectors are induced by B. pertussis-MDDC in the absence of IL-12p70 through an ERK1/2 dependent mechanism, and that p38 MAPK is essential for MDDC-driven Th17 expansion. The data suggest that CyaA mediates an escape strategy for the bacterium, since it reduces Th1 immunity and increases Th17 responses thought to be responsible, when the response is exacerbated, for enhanced lung inflammation and injury.

A polar-drive shock-ignition design for the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Anderson, K. S.; McKenty, P. W.; Collins, T. J. B.; Craxton, R. S.; Delettrez, J. A.; Marozas, J. A.; Skupsky, S.; Shvydky, A. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Betti, R. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Fusion Science Center, University of Rochester, Rochester, New York 14623 (United States); Departments of Mechanical Engineering and Physics, University of Rochester, Rochester, New York 14627 (United States); Hohenberger, M.; Theobald, W.; Lafon, M.; Nora, R. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Fusion Science Center, University of Rochester, Rochester, New York 14623 (United States)

2013-05-15

Shock ignition [R. Betti et al., Phys. Rev. Lett. 98, 155001 (2007)] is being pursued as a viable option to achieve ignition on the National Ignition Facility (NIF). Shock-ignition target designs use a high-intensity laser spike at the end of a low-adiabat assembly pulse to launch a spherically convergent strong shock to ignite the hot spot of an imploding capsule. A shock-ignition target design for the NIF is presented. One-dimensional simulations indicate an ignition threshold factor of 4.1 with a gain of 58. A polar-drive beam-pointing configuration for shock-ignition experiments on the NIF at 750 kJ is proposed. The capsule design is shown to be robust to the various one- and two-dimensional effects and nonuniformities anticipated on the NIF. The target is predicted to ignite with a gain of 38 when including all anticipated levels of nonuniformity and system uncertainty.

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy.

Science.gov (United States)

Gueguen, Claire; Bouley, Julien; Moussu, Hélène; Luce, Sonia; Duchateau, Magalie; Chamot-Rooke, Julia; Pallardy, Marc; Lombardi, Vincent; Nony, Emmanuel; Baron-Bodo, Véronique; Mascarell, Laurent; Moingeon, Philippe

2016-02-01

Regulatory dendritic cell (DC) markers, such as C1Q, are upregulated in PBMCs of patients with grass pollen allergy exhibiting clinical benefit during allergen immunotherapy (AIT). We sought to define markers differentially expressed in human monocyte-derived DCs differentiated toward a proallergic (DCs driving the differentiation of TH2 cells [DC2s]) phenotype and investigate whether changes in such markers in the blood correlate with AIT efficacy. Transcriptomes and proteomes of monocyte-derived DCs polarized toward DCs driving the differentiation of TH1 cells (DC1s), DC2s, or DCs driving the differentiation of regulatory T cells (DCreg cells) profiles were compared by using genome-wide cDNA microarrays and label-free quantitative proteomics, respectively. Markers differentially regulated in DC2s and DCreg cells were assessed by means of quantitative PCR in PBMCs from 80 patients with grass pollen allergy before and after 2 or 4 months of sublingual AIT in parallel with rhinoconjunctivitis symptom scores. We identified 20 and 26 new genes/proteins overexpressed in DC2s and DCreg cells, respectively. At an individual patient level, DC2-associated markers, such as CD141, GATA3, OX40 ligand, and receptor-interacting serine/threonine-protein kinase 4 (RIPK4), were downregulated after a 4-month sublingual AIT course concomitantly with an upregulation of DCreg cell-associated markers, including complement C1q subcomponent subunit A (C1QA), FcγRIIIA, ferritin light chain (FTL), and solute carrier organic anion transporter family member 2B1 (SLCO2B1), in the blood of clinical responders as opposed to nonresponders. Changes in such markers were better correlated with clinical benefit than alterations of allergen-specific CD4(+) T-cell or IgG responses. A combination of 5 markers predominantly expressed by blood DCs (ie, C1Q and CD141) or shared with lymphoid cells (ie, FcγRIIIA, GATA3, and RIPK4) reflecting changes in the balance of regulatory/proallergic responses

Polarization of TH2 response is decreased during pregnancy in systemic lupus erythematosus

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A. Tincani

2012-12-01

Full Text Available This study evaluated some cytokines involved in the Th1-Th2 shift during pregnancy in patients with systemic lupus erythematosus (SLE and healthy women. Twenty-seven consecutive successful pregnancies in 26 SLE patients and 28 pregnancies in 28 matched healthy subjects, as controls, were enrolled and prospectively studied. Sera obtained at first and third trimesters of pregnancy were tested for IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, INF-γ, and TNF-α with a highly sensitive, multiplexed sandwich ELISA (SearchLight Human Inflammatory Cytokine Array. Statistics were performed by SPSS package. IL-8 serum levels were higher in the first (P<0.0001 and third (P=0.003 trimesters of pregnancy in SLE patients compared with controls, INF-γ serum levels in the third trimester (P=0.009, and IL-10 serum levels in the first and third trimesters (P=0.055 and P<0.0001, respectively. IL-2 (r=0.524 P=0.010, IL-12 (r=0.549 P=0.007, IFN-γ (r=0.492 P=0.017, and IL-6 (r=0.515 P=0.020 serum levels correlated with disease activity in SLE patients in the first trimester of pregnancy. Cytokine profile was similar in patients with and without lupus nephritis both in the first and in the third trimesters of pregnancy. IL-8 serum levels were lower in patients with a previous diagnosis of antiphospholipid antibody syndrome compared with those without, both in the first and in the third trimesters of pregnancy. In SLE patients, a lower than expected decrease in Th1 cytokine serum levels was observed in the third trimester of gestation which could contribute to a lower Th2 cytokine polarization during pregnancy.

Climate Drives Polar Bear Origins

Science.gov (United States)

In their provocative analysis of northern bears (“Nuclear genomic sequences reveal that polar bears are an old and distinct bear lineage,” Reports, 20 April, p. 344), F. Hailer et al. use independent nuclear loci to show that polar bears originated during the middle Pleistocene, rather than during t...

Shell effects on the E1 moments of Ra-Th nuclei

International Nuclear Information System (INIS)

Leander, G.A.

1984-01-01

Large systematic shell effects on intrinsic E1 moments are found, which should modulate any E1 moment induced by β 3 deformation. The calculated shell effects can explain an emerging trend for E1 data in Ra-Th nuclei, if and only if the gross β 3 -induced polarization of finite nuclear matter goes in the same direction as the lightning rod effect. 16 references

Oral Administration of p-Hydroxycinnamic Acid Attenuates Atopic Dermatitis by Downregulating Th1 and Th2 Cytokine Production and Keratinocyte Activation.

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Hyun-Su Lee

Full Text Available Atopic dermatitis (AD is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production.

RhIL-11 treatment normalized Th1/Th2 and T-bet/GATA-3 imbalance in in human immune thrombocytopenic purpura (ITP).

Science.gov (United States)

Lin, Ying; Zhou, Xieming; Guo, Wenjian; Li, Qianqian; Pan, Xiahui; Bao, Yunhua; He, Muqing; Zhu, Baoling; Lin, Xiaoji; Jin, Limin; Yao, Rongxin

2016-09-01

Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by reduction in platelet counts. T helper 1 (Th1) cells polarization with an increased shift of Th1/Th2 ratio has been reported in ITP. This shift is associated with transcription factor T-box expressed in T cells (T-bet) upregulation and GATA-binding protein 3 (GATA-3) downregulation, leading to an increased T-bet/GATA-3 ratio. Our previous in vitro study showed that recombinant human interleukin-11 (rhIL-11) could normalize Th1/Th2 imbalance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients, which co-occurred with T-bet/GATA-3 ratio restoration. In this report, we investigated whether rhIL-11 had therapeutic effect in clinical ITP patients and whether rhIL-11 treatment could normalize Th1/Th2 and T-bet/GATA-3 levels in vivo. We found rhIL-11 treatment had a response rate of 67.7% and significantly decreased Th1 and T-bet levels but increased Th2 and GATA-3 levels in ITP patients who showed good response, normalizing Th1/Th2 and T-bet/GATA-3 ratios similar to that in healthy controls. Thus our study suggested rhIL-11 was effective with tolerable adverse effects in ITP. The treatment strategy warrants further clinical investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

VIIRS-J1 Polarization Narrative

Science.gov (United States)

Waluschka, Eugene; McCorkel, Joel; McIntire, Jeff; Moyer, David; McAndrew, Brendan; Brown, Steven W.; Lykke, Keith; Butler, James; Meister, Gerhard; Thome, Kurtis J.

2015-01-01

The VIS/NIR bands polarization sensitivity of Joint Polar Satellite Sensor 1 (JPSS1) Visible/Infrared Imaging Radiometer Suite (VIIRS) instrument was measured using a broadband source. While polarization sensitivity for bands M5-M7, I1, and I2 was less than 2.5%, the maximum polarization sensitivity for bands M1, M2, M3, and M4 was measured to be 6.4%, 4.4%, 3.1%, and 4.3%, respectively with a polarization characterization uncertainty of less than 0.3%. A detailed polarization model indicated that the large polarization sensitivity observed in the M1 to M4 bands was mainly due to the large polarization sensitivity introduced at the leading and trailing edges of the newly manufactured VISNIR bandpass focal plane filters installed in front of the VISNIR detectors. This was confirmed by polarization measurements of bands M1 and M4 bands using monochromatic light. Discussed are the activities leading up to and including the instruments two polarization tests, some discussion of the polarization model and the model results, the role of the focal plane filters, the polarization testing of the Aft-Optics-Assembly, the testing of the polarizers at Goddard and NIST and the use of NIST's T-SIRCUS for polarization testing and associated analyses and results.

5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Alleviates Atherosclerosis via Enhancing Efferocytosis and Facilitating a Shift in the Th1/Th2 Balance Toward Th2 Polarization

Directory of Open Access Journals (Sweden)

Yang Yang

2018-05-01

Full Text Available Background/Aims: We and other groups have demonstrated that 5-aminolevulinic acid (ALA-mediated sonodynamic therapy (ALA-SDT induces macrophage and foam cell apoptosis and stabilizes atherosclerosis (AS plaques in animal models. Lymphocytes also play vital roles in the development of AS. The primary purpose of the present study was to investigate the effects of ALA-SDT on T helper (Th cell fate and function, Th subset differentiation, and atherosclerotic lesion stability. Methods: We utilized ALA-SDT on Western diet-fed apoE-/-mice in vivo and human Jurkat cells in vitro. Hematoxylin and eosin staining and TUNEL assays were used to evaluate the atherosclerotic plaque size and apoptosis within the atheroma. ALA induced cytotoxicity on cultured Jurkat cells was determined with CCK-8 assay. To address the mechanisms, levels of intracellular reactive oxygen species (ROS, mitochondrial membrane potential (MMP, and mitochondrial permeability transition pore (MPTP opening were evaluated by staining with fluorescent probes. Western blot analysis and confocal microscopy were used to analyze the protein levels of caspases, Bax and cytochrome c and the release of cytochrome c. Cell apoptosis and necrosis and phagocytosis were examined by flow cytometry. ELISAs and immunofluorescent staining were used to assess the corresponding cytokine levels and Th subset cell numbers within the atheroma. Results: Our studies revealed that ALA-SDT significantly enhanced CD4+ cell apoptosis and macrophage-mediated phagocytosis and hence reduced the necrotic core size. ALA-SDT activated the mitochondrial apoptotic signaling pathway with minimal necrosis in Jurkat cells. ALA-SDT inhibited the Th1 response and enhanced the Th2 response. These effects of ALA-SDT were mediated primarily through the generation of ROS. Conclusion: ALA-SDT alleviates AS by enhancing cytotoxic effects on Th cells, subsequently stimulating efferocytosis and facilitating a shift in the Th1/Th2

6th international conference on Mars polar science and exploration: Conference summary and five top questions

Science.gov (United States)

Smith, Isaac B.; Diniega, Serina; Beaty, David W.; Thorsteinsson, Thorsteinn; Becerra, Patricio; Bramson, Ali; Clifford, Stephen M.; Hvidberg, Christine S.; Portyankina, Ganna; Piqueux, Sylvain; Spiga, Aymeric; Titus, Timothy N.

2018-01-01

We provide a historical context of the International Conference on Mars Polar Science and Exploration and summarize the proceedings from the 6th iteration of this meeting. In particular, we identify five key Mars polar science questions based primarily on presentations and discussions at the conference and discuss the overlap between some of those questions. We briefly describe the seven scientific field trips that were offered at the conference, which greatly supplemented conference discussion of Mars polar processes and landforms. We end with suggestions for measurements, modeling, and laboratory and field work that were highlighted during conference discussion as necessary steps to address key knowledge gaps.

A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer

Science.gov (United States)

Koski, Gary K.; Koldovsky, Ursula; Xu, Shuwen; Mick, Rosemarie; Sharma, Anupama; Fitzpatrick, Elizabeth; Weinstein, Susan; Nisenbaum, Harvey; Levine, Bruce L; Fox, Kevin; Zhang, Paul; Czerniecki, Brian J

2011-01-01

Twenty-seven subjects with HER-2/neu over-expressing ductal carcinoma in situ of the breast were enrolled in a neoadjuvant immunization trial for safety and immunogenicity of DC1-polarized dendritic cells (DC1) pulsed with six HER-2/neu promiscuous MHC class II-binding peptides, plus two additional HLA-A2.1 class I-binding peptides. DC1 were generated with IFN-γ plus a special clinical-grade bacterial endotoxin (LPS) and administered directly into groin lymph nodes four times at weekly intervals prior to scheduled surgical resection of DCIS. Subjects were monitored for the induction of new or enhanced anti-peptide reactivity by IFN-γ ELIspot and ELISA assays performed on Th cells obtained from peripheral blood or excised sentinel lymph nodes. Responses by CTL against HLA-A2.1-binding peptides were measured using peptide-pulsed T2 target cells or HER-2/neu-expressing or non-expressing tumor cell lines. DC1 showed surface phenotype indistinct from “gold standard” inflammatory cocktail-activated DC, but displayed a number of distinguishing functional characteristics including the secretion of soluble factors and enhanced “killer DC” capacity against tumor cells in vitro. Post-immunization, we observed sensitization of Th cells to at least 1 class II peptide in 22 of 25 (88%, 95% exact CI 68.8 – 97.5%) evaluable subjects, while eleven of 13 (84.6%, 95% exact CI 64 – 99.8%) HLA-A2.1 subjects were successfully sensitized to class I peptides. Perhaps most importantly, anti-HER-2/neu peptide responses were observed up to 52 months post-immunization. These data show even in the presence of early breast cancer such DC1 are potent inducers of durable type I-polarized immunity, suggesting potential clinical value for development of cancer immunotherapy. PMID:22130160

IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation.

Science.gov (United States)

Mitchell, Ruth E; Hassan, Masriana; Burton, Bronwen R; Britton, Graham; Hill, Elaine V; Verhagen, Johan; Wraith, David C

2017-09-12

IL-10 is an immunomodulatory cytokine with a critical role in limiting inflammation in immune-mediated pathologies. The mechanisms leading to IL-10 expression by CD4 + T cells are being elucidated, with several cytokines implicated. We explored the effect of IL-4 on the natural phenomenon of IL-10 production by a chronically stimulated antigen-specific population of differentiated Th1 cells. In vitro, IL-4 blockade inhibited while addition of exogenous IL-4 to Th1 cultures enhanced IL-10 production. In the in vivo setting of peptide immunotherapy leading to a chronically stimulated Th1 phenotype, lack of IL-4Rα inhibited the induction of IL-10. Exploring the interplay of Th1 and Th2 cells through co-culture, Th2-derived IL-4 promoted IL-10 expression by Th1 cultures, reducing their pathogenicity in vivo. Co-culture led to upregulated c-Maf expression with no decrease in the proportion of T-bet + cells in these cultures. Addition of IL-4 also reduced the encephalitogenic capacity of Th1 cultures. These data demonstrate that IL-4 contributes to IL-10 production and that Th2 cells modulate Th1 cultures towards a self-regulatory phenotype, contributing to the cross-regulation of Th1 and Th2 cells. These findings are important in the context of Th1 driven diseases since they reveal how the Th1 phenotype and function can be modulated by IL-4.

Langerhans cell-like dendritic cells stimulated with an adjuvant direct the development of Th1 and Th2 cells in vivo.

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Matsui, K; Mori, A; Ikeda, R

2015-10-01

It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of immune responses towards a T helper type 1 (Th1) or Th2 milieu. In this study, we attempted to generate LCs from murine bone marrow cells and elicit a Th1- or Th2-prone immune response through the LCs after stimulation with Th1 or Th2 adjuvant. LCs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and transforming growth factor (TGF)-β, and were obtained as I-A(d) positive cells. Mice were primed with Th1/Th2 adjuvant- and ovalbumin (OVA)-pulsed LCs and then given a booster injection of OVA 2 days later via the hind footpad. Five days after the OVA injection, the cytokine response in the draining popliteal lymph nodes was investigated by reverse transcription-polymerase chain reaction (RT-PCR) flow cytometry and enzyme-linked immunosorbent assay (ELISA). The generated LCs expressed typical LC surface markers, E-cadherin and Langerin, and were classified accordingly as LC-like dendritic cells (LDCs). Administration of Th1 adjuvant, cytosine-phosphate-guanosine (CpG)-DNA- and OVA-pulsed LDCs into the hind footpads of mice induced a Th1-prone immune response, as represented by up-regulation of IFN-γ production and down-regulation of IL-4 production in the lymph node cells. Conversely, Th2 adjuvant, histamine-pulsed LDCs induced a Th2-prone immune response, as represented by up-regulation of IL-4 production and down-regulation of IFN-γ production. These results suggest that LDCs may be used as a substitute for LCs and have the ability to induce the development of Th1 and Th2 cells in vivo. Our experimental system would therefore be useful for screening of inhibitors of Th1/Th2 differentiation in order to control allergic disease. © 2015 British Society for Immunology.

Evaluation of the Revolver Ignition Design at the National Ignition Facility Using Polar-Direct-Drive Illumination

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McKenty, P. W.; Collins, T. J. B.; Marozas, J. A.; Campbell, E. M.; Molvig, K.; Schmitt, M.

2017-10-01

The direct-drive ignition design Revolver employs a triple-shell target using a beryllium ablator, a copper driver, and an eventual gold pusher. Symmetric numerical calculations indicate that each of the three shells exhibit low convergence ( 3to 5) resulting in a modest gain (G 4) for 1.7 MJ of incident laser energy. Studies are now underway to evaluate the robustness of this design employing polar direct drive (PDD) at the National Ignition Facility. Integral to these calculations is the leveraging of illumination conditioning afforded by research done to demonstrate ignition for a traditional PDD hot-spot target design. Two-dimensional simulation results, employing nonlocal electron-thermal transport and cross-beam energy transport, will be presented that indicate ignition using PDD. A study of the allowed levels of long-wavelength perturbations (target offset and power imbalance) not precluding ignition will also be examined. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

Th1/Th2 cytokine expression in diabetic retinopathy.

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Cao, Y L; Zhang, F Q; Hao, F Q

2016-07-15

Diabetic retinopathy (DR), an important complication of diabetes mellitus (DM), is not well understood. T helper cell balance (Th1/Th2) is involved in various autoimmune diseases; however, its role in DR is not understood. This study explores changes in Th1 and Th2 cytokine expression during DR. Blood samples were collected from 25 healthy volunteers (normal control group), 35 patients with type 2 DM (T2DM group) without DR, and 30 cases of T2DM patients with DR (DR group). Real-time PCR was used to measure mRNA expression of IL-2 and TNF-α, secreted from Th1 cells, and of IL-4 and IL-10, secreted from Th2 cells. We used ELISA to detect cytokine expression in serum to analyze the correlation between Th1 and Th2 cytokines. IL-2 and TNF-αmRNA and protein expression levels in the T2DM and DR groups were significantly higher than in the normal control group (P 0.05). IL-2 and TNF-αwere negatively correlated with IL-4 and IL-10 in the DR group, respectively. We found that Th1 cytokine secretion was higher and Th2 cytokines secretion was lower during DR, leading to a Th1/ Th2 imbalance, suggesting that Th1/Th2 imbalance is a side effect for DR occurrence and development.

Th1/M1 conversion to Th2/M2 responses in models of inflammation lacking cell death stimulates maturation of monocyte precursors to fibroblasts

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JoAnn eTrial

2013-09-01

Full Text Available We have demonstrated that cardiac fibrosis arises from the differentiation of monocyte-derived fibroblasts. We present here evidence that this process requires sequential Th1 and Th2 induction promoting analogous M1 (classically activated and M2 (alternatively activated macrophage polarity. Our models are 1 mice subjected to daily repetitive ischemia reperfusion (I/R without infarction and 2 the in vitro transmigration of human mononuclear leukocytes through human cardiac microvascular endothelium. In the mouse heart, leukocytes entered after I/R in response to monocyte chemoattractant protein-1 (MCP-1 which is the major cytokine induced by this protocol. Monocytes within the heart then differentiated into fibroblasts making collagen while bearing the markers of M2 macrophages. T cells were seen in these hearts as well as in the human heart with cardiomyopathy. In the in vitro model, transmigration of the leukocytes was likewise induced by MCP-1 and some monocytes matured into fibroblasts bearing M2 markers. In this model, the MCP-1 stimulus induced a transient Th1 and M1 response that developed into a predominately Th2 and M2 response. An increase in the Th2 product IL-13 was present in both the human and the mouse models, consistent with its known role in fibrosis. In these simplified models, in which there is no cell death to stimulate an anti-inflammatory response, there is nonetheless a resolution of inflammation enabling a profibrotic environment. This induces the maturation of monocyte precursors into fibroblasts.

Ecological change drives a decline in mercury concentrations in southern Beaufort Sea polar bears

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McKinney, Melissa A.; Atwood, Todd C.; Pedro, Sara; Peacock, Elizabeth

2017-01-01

We evaluated total mercury (THg) concentrations and trends in polar bears from the southern Beaufort Sea subpopulation from 2004 to 2011. Hair THg concentrations ranged widely among individuals from 0.6 to 13.3 μg g–1 dry weight (mean: 3.5 ± 0.2 μg g–1). Concentrations differed among sex and age classes: solitary adult females ≈ adult females with cubs ≈ subadults > adult males ≈ yearlings > cubs-of-the-year ≈ 2 year old dependent cubs. No variation was observed between spring and fall samples. For spring-sampled adults, THg concentrations declined by 13% per year, contrasting recent trends observed for other Western Hemispheric Arctic biota. Concentrations also declined by 15% per year considering adult males only, while a slower, nonsignificant decrease of 4.4% per year was found for adult females. Lower THg concentrations were associated with higher body mass index (BMI) and higher proportions of lower trophic position food resources consumed. Because BMI and diet were related, and the relationship to THg was strongest for BMI, trends were re-evaluated adjusting for BMI as the covariate. The adjusted annual decline was not significant. These findings indicate that changes in foraging ecology, not declining environmental concentrations of mercury, are driving short-term declines in THg concentrations in southern Beaufort Sea polar bears.

Quantitative Proteomics of Gut-Derived Th1 and Th1/Th17 Clones Reveal the Presence of CD28+ NKG2D- Th1 Cytotoxic CD4+ T cells.

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Riaz, Tahira; Sollid, Ludvig Magne; Olsen, Ingrid; de Souza, Gustavo Antonio

2016-03-01

T-helper cells are differentiated from CD4+ T cells and are traditionally characterized by inflammatory or immunosuppressive responses in contrast to cytotoxic CD8+ T cells. Mass-spectrometry studies on T-helper cells are rare. In this study, we aimed to identify the proteomes of human Th1 and Th1/Th17 clones derived from intestinal biopsies of Crohn's disease patients and to identify differentially expressed proteins between the two phenotypes. Crohn's disease is an inflammatory bowel disease, with predominantly Th1- and Th17-mediated response where cells of the "mixed" phenotype Th1/Th17 have also been commonly found. High-resolution mass spectrometry was used for protein identification and quantitation. In total, we identified 7401 proteins from Th1 and Th1/Th17 clones, where 334 proteins were differentially expressed. Major differences were observed in cytotoxic proteins that were overrepresented in the Th1 clones. The findings were validated by flow cytometry analyses using staining with anti-granzyme B and anti-perforin and by a degranulation assay, confirming higher cytotoxic features of Th1 compared with Th1/Th17 clones. By testing a larger panel of T-helper cell clones from seven different Crohn's disease patients, we concluded that only a subgroup of the Th1 cell clones had cytotoxic features, and these expressed the surface markers T-cell-specific surface glycoprotein CD28 and were negative for expression of natural killer group 2 member D. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Real-time multi-target ranging based on chaotic polarization laser radars in the drive-response VCSELs.

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Zhong, Dongzhou; Xu, Geliang; Luo, Wei; Xiao, Zhenzhen

2017-09-04

According to the principle of complete chaos synchronization and the theory of Hilbert phase transformation, we propose a novel real-time multi-target ranging scheme by using chaotic polarization laser radar in the drive-response vertical-cavity surface-emitting lasers (VCSELs). In the scheme, to ensure each polarization component (PC) of the master VCSEL (MVCSEL) to be synchronized steadily with that of the slave VCSEL, the output x-PC and y-PC from the MVCSEL in the drive system and those in the response system are modulated by the linear electro-optic effect simultaneously. Under this condition, by simulating the influences of some key parameters of the system on the synchronization quality and the relative errors of the two-target ranging, related operating parameters can be optimized. The x-PC and the y-PC, as two chaotic radar sources, are used to implement the real-time ranging for two targets. It is found that the measured distances of the two targets at arbitrary position exhibit strong real-time stability and only slight jitter. Their resolutions are up to millimeters, and their relative errors are very small and less than 2.7%.

Ex-Th17 (Nonclassical Th1) Cells Are Functionally Distinct from Classical Th1 and Th17 Cells and Are Not Constrained by Regulatory T Cells.

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Basdeo, Sharee A; Cluxton, Deborah; Sulaimani, Jamal; Moran, Barry; Canavan, Mary; Orr, Carl; Veale, Douglas J; Fearon, Ursula; Fletcher, Jean M

2017-03-15

Th17 cells are an important therapeutic target in autoimmunity. However, it is known that Th17 cells exhibit considerable plasticity, particularly at sites of autoimmune inflammation. Th17 cells can switch to become ex-Th17 cells that no longer produce IL-17 but produce IFN-γ. These ex-Th17 cells are also called nonclassical Th1 cells because of their ability to produce IFN-γ, similar to Th1 cells; however, it is unclear whether they resemble Th1 or Th17 cells in terms of their function and regulation, and whether they have a pathogenic role in autoimmunity. We compared the phenotypic and functional features of human Th17, Th1, and ex-Th17 cell populations. Our data showed that despite their loss of IL-17 expression, ex-Th17 cells were more polyfunctional in terms of cytokine production than either Th1 or bona fide Th17 cells, and produced increased amounts of proinflammatory cytokines. The proliferative brake on Th17 cells appeared to be lifted because ex-Th17 cells proliferated more than Th17 cells after stimulation. In contrast with Th1 and Th17 cells, ex-Th17 cells were highly resistant to suppression of proliferation and cytokines by regulatory T cells. Finally, we showed that ex-Th17 cells accumulated in the joints of rheumatoid arthritis patients. Taken together, these data indicate that human ex-Th17 cells are functionally distinct from Th1 and Th17 cells, and suggest that they may play a pathogenic role at sites of autoimmunity, such as the rheumatoid arthritis joint where they accumulate. These findings have implications for therapeutic strategies that target IL-17, because these may not inhibit pathogenic ex-Th17 cells. Copyright © 2017 by The American Association of Immunologists, Inc.

H1 antihistamines and driving.

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Popescu, Florin Dan

2008-01-01

Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion. Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one.

A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2.

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Shi, Qian; Wang, Qiu; Li, Jing; Zhou, Xiaohui; Fan, Huimin; Wang, Fenghua; Liu, Haiyun; Sun, Xiangjun; Sun, Xiaodong

2015-12-01

Inflammatory status of RPE cells induced by A2E is essential in the development of AMD. Recent research indicated T-cell immunity was involved in the pathological progression of AMD. This study was designed to investigate how A2E suppresses immunoregulatory function of RPE cells in T-cell immunity in vitro. Mouse RPE cells or human ARPE19 cells were stimulated with A2E, and co-cultured with naïve T cells under Th1, Th2, Th17, and regulatory T cell (Treg) polarization conditions. The intracellular cytokines or transcript factors of the induced T-cells subset were detected with flow cytometer and qRT-PCR. The ROS levels were detected, and the factors and possible pathways involved in the A2E-laden RPE cells were analyzed through neutralization antibody of IL-1β and inhibitors of related pathways. The A2E reduced regulatory function of RPE cells in Treg differentiation. The A2E-laden RPE cells promoted polarization of Th1 cells in vitro, but not Th2 or Th17 differentiation. The A2E induced RPE cells to release inflammatory cytokines and ROS, but PGE2 production was inhibited. Through neutralization of IL-1β or inhibition of COX2-PGE2 pathways, A2E-laden RPE cells expressed reduced effect in inducing Th1 cells. The A2E inhibited regulatory function of RPE cells in suppressing Th1 cell immunity in vitro through production of IL-1β and inhibition of PGE2. Our data indicate that A2E could suppress immunoregulatory function of RPE cells and adaptive immunity might play a role in the immune pathogenesis of AMD.

Delayed Activation Kinetics of Th2- and Th17 Cells Compared to Th1 Cells.

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Duechting, Andrea; Przybyla, Anna; Kuerten, Stefanie; Lehmann, Paul V

2017-09-12

During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune monitoring purposes. Antigen-specific Th1, Th2, and Th17 cells can be detected by challenging peripheral blood mononuclear cells (PBMC) with antigen, and establishing the numbers of T cells producing the respective lead cytokine, IFN-γ and IL-2 for Th1 cells, IL-4 and IL-5 for Th2, and IL-17 for Th-17 cells, respectively. Traditionally, these cytokines are measured within 6 h in flow cytometry. We show here that 6 h of stimulation is sufficient to detect peptide-induced production of IFN-γ, but 24 h are required to reveal the full frequency of protein antigen-specific Th1 cells. Also the detection of IL-2 producing Th1 cells requires 24 h stimulation cultures. Measurements of IL-4 producing Th2 cells requires 48-h cultures and 96 h are required for frequency measurements of IL-5 and IL-17 secreting T cells. Therefore, accounting for the differential secretion kinetics of these cytokines is critical for the accurate determination of the frequencies and ratios of antigen-specific Th1, Th2, and Th17 cells.

Competition for Antigen between Th1 and Th2 Responses Determines the Timing of the Immune Response Switch during Mycobaterium avium Subspecies paratuberulosis Infection in Ruminants

Science.gov (United States)

Magombedze, Gesham; Eda, Shigetoshi; Ganusov, Vitaly V.

2014-01-01

Johne's disease (JD), a persistent and slow progressing infection of ruminants such as cows and sheep, is caused by slow replicating bacilli Mycobacterium avium subspecies paratuberculosis (MAP) infecting macrophages in the gut. Infected animals initially mount a cell-mediated CD4 T cell response against MAP which is characterized by the production of interferon (Th1 response). Over time, Th1 response diminishes in most animals and antibody response to MAP antigens becomes dominant (Th2 response). The switch from Th1 to Th2 response occurs concomitantly with disease progression and shedding of the bacteria in feces. Mechanisms controlling this Th1/Th2 switch remain poorly understood. Because Th1 and Th2 responses are known to cross-inhibit each other, it is unclear why initially strong Th1 response is lost over time. Using a novel mathematical model of the immune response to MAP infection we show that the ability of extracellular bacteria to persist outside of macrophages naturally leads to switch of the cellular response to antibody production. Several additional mechanisms may also contribute to the timing of the Th1/Th2 switch including the rate of proliferation of Th1/Th2 responses at the site of infection, efficiency at which immune responses cross-inhibit each other, and the rate at which Th1 response becomes exhausted over time. Our basic model reasonably well explains four different kinetic patterns of the Th1/Th2 responses in MAP-infected sheep by variability in the initial bacterial dose and the efficiency of the MAP-specific T cell responses. Taken together, our novel mathematical model identifies factors of bacterial and host origin that drive kinetics of the immune response to MAP and provides the basis for testing the impact of vaccination or early treatment on the duration of infection. PMID:24415928

Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.

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Iris J Gonzalez-Leal

2014-09-01

Full Text Available Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb and L (Ctsl play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrophages play during Leishmania infection, we generated bone-marrow derived dendritic cells (BMDC and macrophages (BMM from Ctsb-/- and Ctsl-/- mice, and studied the effects of Ctsb and Ctsl deficiency on the survival of L. major in infected cells. Furthermore, the signals used by dendritic cells to instruct Th cell polarization were addressed: the expression of MHC class II and co-stimulatory molecules, and cytokine production. We found that Ctsb-/- BMDC express higher levels of MHC class II molecules than wild-type (WT and Ctsl-/- BMDC, while there were no significant differences in the expression of co-stimulatory molecules between cathepsin-deficient and WT cells. Moreover, both BMDC and BMM from Ctsb-/- mice significantly up-regulated the levels of interleukin 12 (IL-12 expression, a key Th1-inducing cytokine. These findings indicate that Ctsb-/- BMDC display more pro-Th1 properties than their WT and Ctsl-/- counterparts, and therefore suggest that Ctsb down-regulates the Th1 response to L. major. Moreover, they propose a novel role for Ctsb as a regulator of cytokine expression.

A Built-In CpG Adjuvant in RSV F Protein DNA Vaccine Drives a Th1 Polarized and Enhanced Protective Immune Response

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Yao Ma

2018-01-01

Full Text Available Human respiratory syncytial virus (RSV is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F glycoprotein on the vaccine-induced immune response. The addition of CpG-C motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c mice immunized with the DNA vaccines. Moreover, mice vaccinated with CpG-modified vaccines, especially with the higher 20 copies, resulted in an enhanced shift toward a Th1-biased antibody and T-cell response, a decrease in pulmonary pathology and virus replication, and a decrease in weight loss after RSV challenge. This study suggests that CpG-C motif, cloned into the backbone of DNA vaccine encoding RSV F glycoprotein, functions as a built-in adjuvant capable of improving the efficacy of DNA vaccine against RSV infection.

Th1-, Th2-, and Th17-associated cytokine expression in hypopharyngeal carcinoma and clinical significance.

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Chen, Xuemei; Wang, Junfu; Wang, Rui; Su, Qinghong; Luan, Junwen; Huang, Haiyan; Zhou, Peng; Liu, Jinsheng; Xu, Xiaoqun

2016-02-01

Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells, have been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 53 patients with hypopharyngeal cancer were included. The expression levels of Th1-, Th2- and Th17-associated cytokines in hypopharyngeal cancer tissues and pericarcinoma tissues were detected. The relationship between Th1, Th2, or Th17 infiltration and metastasis was studied. Our results showed that the mRNA and protein expressions of Th1 cytokines were lower, while the expressions of Th2 and Th17 cytokines were higher in tumor tissues, and the intensity of expression was strengthened with clinical stage increasing. Cancer tissues had higher level expressions of Th2 and Th17 cytokines than that of pericarcinoma tissues. From the above data, we speculated that high expressions of Th2- and Th17-associated cytokines in hypopharyngeal carcinoma may contribute to cancer development and metastasis.

Th1 and Th2 help for B cells

DEFF Research Database (Denmark)

Poudrier, J; Owens, T

1995-01-01

that IL-5 (125 U/ml) synergizes with Th1 cells to induce B cell responses to IL-2, that are maintained following T-cell removal, e.g. autonomous. Th1 help in the absence of IL-5 resulted in weak or undetectable responses following T cell removal. The mechanism of IL-5 synergy involved persistence of IL-2R...... anti-Ig did not circumvent the need for IL-5 for autonomous IL-2 responses. Consistent with the above, interaction with an IL-5-producing Th2 clone induced strong autonomous B cell responses to IL-2. Qualitative differences of Th2 help over that of Th1 may thus be attributable to their differential...

Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

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Chen-Chen Lee

2015-01-01

Full Text Available This study investigated the immunomodulatory effects of ferulic acid (FA on antigen-presenting dendritic cells (DCs in vitro and its antiallergic effects against ovalbumin- (OVA- induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS stimulation induced a high level of interleukin- (IL- 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF- α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4, MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13, and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN- γ production in bronchoalveolar lavage fluid (BALF and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses.

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Baumann, Claudia; Bonilla, Weldy V; Fröhlich, Anja; Helmstetter, Caroline; Peine, Michael; Hegazy, Ahmed N; Pinschewer, Daniel D; Löhning, Max

2015-03-31

During infection, the release of damage-associated molecular patterns, so-called "alarmins," orchestrates the immune response. The alarmin IL-33 plays a role in a wide range of pathologies. Upon release, IL-33 signals through its receptor ST2, which reportedly is expressed only on CD4(+) T cells of the Th2 and regulatory subsets. Here we show that Th1 effector cells also express ST2 upon differentiation in vitro and in vivo during lymphocytic choriomeningitis virus (LCMV) infection. The expression of ST2 on Th1 cells was transient, in contrast to constitutive ST2 expression on Th2 cells, and marked highly activated effector cells. ST2 expression on virus-specific Th1 cells depended on the Th1-associated transcription factors T-bet and STAT4. ST2 deficiency resulted in a T-cell-intrinsic impairment of LCMV-specific Th1 effector responses in both mixed bone marrow-chimeric mice and adoptive cell transfer experiments. ST2-deficient virus-specific CD4(+) T cells showed impaired expansion, Th1 effector differentiation, and antiviral cytokine production. Consequently, these cells mediated little virus-induced immunopathology. Thus, IL-33 acts as a critical and direct cofactor to drive antiviral Th1 effector cell activation, with implications for vaccination strategies and immunotherapeutic approaches.

What about Th1/Th2 in cutaneous leishmaniasis vaccine discovery?

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Campos-Neto A.

2005-01-01

Full Text Available The T helper cell type 1 (Th1 response is essential to resist leishmaniasis, whereas the Th2 response favors the disease. However, many leishmanial antigens, which stimulate a Th1 immune response during the disease or even after the disease is cured, have been shown to have no protective action. Paradoxically, antigens associated with an early Th2 response have been found to be highly protective if the Th1 response to them is generated before infection. Therefore, finding disease-associated Th2 antigens and inducing a Th1 immune response to them using defined vaccination protocols is an interesting unorthodox alternative approach to the discovery of a leishmania vaccine.

Interferon-β Suppresses Murine Th1 Cell Function in the Absence of Antigen-Presenting Cells

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Boivin, Nicolas; Baillargeon, Joanie; Doss, Prenitha Mercy Ignatius Arokia; Roy, Andrée-Pascale; Rangachari, Manu

2015-01-01

Interferon (IFN)-β is a front-line therapy for the treatment of the relapsing-remitting form of multiple sclerosis. However, its immunosuppressive mechanism of function remains incompletely understood. While it has been proposed that IFN-β suppresses the function of inflammatory myelin antigen-reactive T cells by promoting the release of immunomodulatory cytokines such as IL-27 from antigen-presenting cells (APCs), its direct effects on inflammatory CD4+ Th1 cells are less clear. Here, we establish that IFN-β inhibits mouse IFN-γ+ Th1 cell function in the absence of APCs. CD4+ T cells express the type I interferon receptor, and IFN-β can suppress Th1 cell proliferation under APC-free stimulation conditions. IFN-β-treated myelin antigen-specific Th1 cells are impaired in their ability to induce severe experimental autoimmune encephalomyelitis (EAE) upon transfer to lymphocyte-deficient Rag1-/- mice. Polarized Th1 cells downregulate IFN-γ and IL-2, and upregulate the negative regulatory receptor Tim-3, when treated with IFN-β in the absence of APCs. Further, IFN-β treatment of Th1 cells upregulates phosphorylation of Stat1, and downregulates phosphorylation of Stat4. Our data indicate that IFN-γ-producing Th1 cells are directly responsive to IFN-β and point to a novel mechanism of IFN-β-mediated T cell suppression that is independent of APC-derived signals. PMID:25885435

Activated rat hepatic stellate cells influence Th1/Th2 profile in vitro.

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Xing, Zhi-Zhi; Huang, Liu-Ye; Wu, Cheng-Rong; You, Hong; Ma, Hong; Jia, Ji-Dong

2015-06-21

To investigate the effects of activated rat hepatic stellate cells (HSCs) on rat Th1/Th2 profile in vitro. Growth and survival of activated HSCs and CD4(+) T lymphocytes cultured alone or together was assessed after 24 or 48 h. CD4(+) T lymphocytes were then cultured with or without activated HSCs for 24 or 48 h and the proportion of Th1 [interferon (IFN)-γ(+)] and Th2 [interleukin (IL)-4(+)] cells was assessed by flow cytometry. Th1 and Th2 cell apoptosis was assessed after 24 h of co-culture using a caspase-3 staining procedure. Differentiation rates of Th1 and Th2 cells from CD4(+) T lymphocytes that were positive for CD25 but did not express IFN-γ or IL-4 were also assessed after 48 h of co-culture with activated HSCs. Galectin-9 expression in HSCs was determined by immunofluorescence and Western blotting. ELISA was performed to assess galectin-9 secretion from activated HSCs. Co-culture of CD4(+) T lymphocytes with activated rat HSCs for 48 h significantly reduced the proportion of Th1 cells compared to culture-alone conditions (-1.73% ± 0.71%; P Th1/Th2 ratio was significantly decreased (-0.44 ± 0.13; P Th1 cells was decreased (-65.71 ± 9.67; P Th1 (12.27% ± 0.99%; P Th1 cell apoptosis rate was significantly higher than in Th2 cells (P Th1 and Th2 cells; however, the increase in the proportion of Th2 cells was significantly higher than that of Th1 cells (1.85% ± 0.48%; P Th1/Th2 profile, inhibiting the Th1 response and enhancing the Th2 response, and this may be a novel pathway for liver fibrogenesis.

ACTIVITY OF LICHENS UNDER THE INFLUENCE OF SNOW AND ICE (18th Symposium on Polar Biology)

OpenAIRE

Ludger, KAPPEN; Burkhard, SCHROETER

1997-01-01

A major aim of our investigations is to explain the adaptation of vegetation to the peculiar environmental conditions in polar regions. Our concept describes the main limiting and favorable factors influencing photosynthetic production of cryptogams, mainly lichens. Snow and ice-usually stress factors to the activity of plants-can be effectively used by lichens because of their poikilohydrous nature. Light, the basic driving force for photosynthetic activity, may be deleterious under certain ...

Photoinduced electron transfer in covalent ruthenium-anthraquinone dyads: relative importance of driving-force, solvent polarity, and donor-bridge energy gap.

Science.gov (United States)

Hankache, Jihane; Wenger, Oliver S

2012-02-28

Four rigid rod-like molecules comprised of a Ru(bpy)(3)(2+) (bpy = 2,2'-bipyridine) photosensitizer, a 9,10-anthraquinone electron acceptor, and a molecular bridge connecting the two redox partners were synthesized and investigated by optical spectroscopic and electrochemical means. An attempt was made to assess the relative importance of driving-force, solvent polarity, and bridge variation on the rates of photoinduced electron transfer in these molecules. Expectedly, introduction of tert-butyl substituents in the bipyridine ligands of the ruthenium complex and a change in solvent from dichloromethane to acetonitrile lead to a significant acceleration of charge transfer rates. In dichloromethane, photoinduced electron transfer is not competitive with the inherent excited-state deactivation processes of the photosensitizer. In acetonitrile, an increase in driving-force by 0.2 eV through attachment of tert-butyl substituents to the bpy ancillary ligands causes an increase in electron transfer rates by an order of magnitude. Replacement of a p-xylene bridge by a p-dimethoxybenzene spacer entails an acceleration of charge transfer rates by a factor of 3.5. In the dyads from this study, the relative order of importance of individual influences on electron transfer rates is therefore as follows: solvent polarity ≥ driving-force > donor-bridge energy gap.

Cholera Toxin Promotes Th17 Cell Differentiation by Modulating Expression of Polarizing Cytokines and the Antigen-Presenting Potential of Dendritic Cells.

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Kang, Jung-Ok; Lee, Jee-Boong; Chang, Jun

2016-01-01

Cholera toxin (CT), an exotoxin produced by Vibrio cholera, acts as a mucosal adjuvant. In a previous study, we showed that CT skews differentiation of CD4 T cells to IL-17-producing Th17 cells. Here, we found that intranasal administration of CT induced migration of migratory dendritic cell (DC) populations, CD103+ DCs and CD11bhi DCs, to the lung draining mediastinal lymph nodes (medLN). Among those DC subsets, CD11bhi DCs that were relatively immature had a major role in Th17 cell differentiation after administration of CT. CT-treated BMDCs showed reduced expression of MHC class II and CD86, similar to CD11bhi DCs in medLN, and these BMDCs promoted Th17 cell differentiation more potently than other BMDCs expressing higher levels of MHC class II and CD86. By analyzing the expression of activation markers such as CD25 and CD69, proliferation and IL-2 production, we determined that CT-treated BMDCs showed diminished antigen-presenting potential to CD4+ T cells compared with normal BMDCs. We also found that CT-stimulated BMDCs promote activin A expression as well as IL-6 and IL-1β, and activin A had a synergic role with TGF-β1 in CT-mediated Th17 cell differentiation. Taken together, our results suggest that CT-stimulated DCs promote Th17 cell differentiation by not only modulating antigen-presenting potential but also inducing Th polarizing cytokines.

Monocyte-derived dendritic cells exposed to Der p 1 allergen enhance the recruitment of Th2 cells: major involvement of the chemokines TARC/CCL17 and MDC/CCL22

NARCIS (Netherlands)

Hammad, Hamida; Smits, Hermelijn H.; Ratajczak, Céline; Nithiananthan, Asokananthan; Wierenga, Eddy A.; Stewart, Geoffrey A.; Jacquet, Alain; Tonnel, Andre-Bernard; Pestel, Joël

2003-01-01

Dendritic cells (DC) are potent antigen - presenting cells that can orientate the immune response towards a Th1 or a Th2 type. DC produce chemokines that are involved in the recruitment of either Th1 cells, such as IP10 (CXCL10), Th2 cells such as TARC (CCL17) and MDC (CCL22), or non-polarized T

Th1-Th17 Ratio as a New Insight in Rheumatoid Arthritis Disease.

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Bazzazi, Hadi; Aghaei, Mehrdad; Memarian, Ali; Asgarian-Omran, Hossein; Behnampour, Nasser; Yazdani, Yaghoub

2018-02-01

The Th17, Th1 and dual Th17/Th1 cells are important players in rheumatoid arthritis (RA) disease. To assess their roles, the frequency and impact of these cells were investigated in patients with different disease activity. In 14 new cases and 41 established RA patients in comparison with 22 healthy controls, the percentages of Th17, Th1 and dual Th17/Th1 cells were determined by flow-cytometry and their correlations were investigated with disease activity score (DAS28). Moreover, serum levels of IL-6 and IL-17 as inducer and functional cytokines for Th17 were investigated. Finally, serum levels of anti citrullinated protein antibody (ACPA) and rheumatoid factor (RF) were assessed. Percentage of Th17 cells in RA patients were increased in comparison with healthy controls (pTh1 cells in RA patients were less than healthy group (pTh17/Th1 cell only in new cases of RA were more than healthy control groups (pTh1/Th17 ratio in RA patients is statistically different with healthy control group (pTh1/Th17 ratio in RA patient suggested a new paradigm in the field of autoimmune disease and indicated that imbalance or plasticity between these subsets can be important in progress, diagnosis and therapy of RA disease.

Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

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Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

Polarized Th2 like cells, in the absence of Th0 cells, are responsible for lymphocyte produced IL-4 in high IgE-producer schistosomiasis patients

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Soares-Silveira Alda

2002-07-01

Full Text Available Abstract Background Human resistance to re-infection with S. mansoni is correlated with high levels of anti-soluble adult worm antigens (SWAP IgE. Although it has been shown that IL-4 and IL-5 are crucial in establishing IgE responses in vitro, the active in vivo production of these cytokines by T cells, and the degree of polarization of Th2 vs. Th0 in human schistosomiasis is not known. To address this question, we determined the frequency of IL-4 and IFN-γ or IL-5 and IL-2 producing lymphocytes from schistosomiasis patients with high or low levels of IgE anti-SWAP. Results Our analysis showed that high and low IgE-producers responded equally to schistosomiasis antigens as determined by proliferation. Moreover, patients from both groups displayed similar percentages of circulating lymphocytes. However, high IgE-producers had an increased percentage of activated CD4+ T cells as compared to the low IgE-producers. Moreover, intracellular cytokine analysis, after short-term stimulation with anti-CD3/CD28 mAbs, showed that IgE high-producers display an increase in the percentage of T lymphocytes expressing IL-4 and IL-5 as compared to IgE low-responders. A coordinate control of the frequency of IL-4 and IL-5 producing lymphocytes in IgE high, but not IgE low-responders, was observed. Conclusions High IgE phenotype human schistosomiasis patients exhibit a coordinate regulation of IL-4 and IL-5 producing cells and the lymphocyte derived IL-4 comes from true polarized Th2 like cells, in the absence of measurable Th0 cells as measured by co-production of IL-4 and IFN-γ.

Implementing SPRINTT [Student Polar Research with IPY National(and International)Teacher Training] in 5th Grade Science

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Glass, D. S.

2009-12-01

I implemented the new NSF-funded SPRINTT (Student Polar Research with IPY National (and International) Teacher Training) curriculum with a 5th grade science class. SPRINTT, developed at U.S. Satellite Laboratory, Inc., is a 5-8 week science program teaching 5th through 10th graders to investigate climate change using polar data. The program includes perspectives of both Western scientists and the indigenous Northern population. The course contains three phases: Phase 1 includes content, data interpretation, and hands-on experiments to study Frozen Water, Frozen Land, and Food; Phase 2 (optional) includes further content on specific polar topics; and Phase 3 is a scaffolded research investigation. Before the course, teachers were trained via live webinars. This curriculum capitalizes on children’s innate fascination with our planet’s final frontier and combines it with the politically and scientifically relevant topic of climate change. In 2009, I used SPRINTT with 23 heterogeneous fifth grade students at National Presbyterian School in Washington DC for an environmental science unit. Overall, it was a success. The students met most of the learning objectives and showed enthusiasm for the material. I share my experiences to help other educators and curriculum developers. The Phase 1 course includes earth science (glaciers, sea ice, weather and climate, greenhouse gases, seasons, and human impacts on environments), life science (needs of living things, food and energy transfer, adaptations, and ecosystems and biomes) and physical science (phases of matter). Tailoring the program, I focused on Phase 1, the most accessible material and content, while deemphasizing the more cumbersome Phase 3 online research project. Pre-assessments documented the students’ misconceptions and informed instruction. The investigations were appropriately educational and interesting. For example, students enjoyed looking at environmental factors and their impact on the people in the

EMT factor Zeb1 depletion in dendritic cells enhances Helminth clearance in mice by increasing Th2 cell differentiation

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Shuchi Smita

2017-10-01

Full Text Available Dendritic cells are professional antigen presenting cells that act as bridging link between innate and adaptive immune system. They are equipped with pathogen recognition receptors (PRR to identify the pathogen associated molecular pattern (PAMPS on any antigen. DCs elicit an immune response through polarizing T cells towards various subtypes like Th1, Th2 & Tregs. Though DC-T cell interaction has been widely studied, but how this single DC molecule amalgamate various transcriptional signals for translating the message to the T cells and induce diverse immunological responses still needs to be unraveled. Therefore to identify the role of transcription factor in immune programming we have targeted the largest member of TFs family, Zinc Finger Transcription Factors (ZF-TFs. Among various ZF-TFs we have narrowed our study to three interesting candidates Zeb1, Zeb2 and Zbtb10 based on their expression in DCs from an unpublished microarray data. Here in this study we have tried to understand the role of Zeb1, master regulator of EMT program in orchestrating DC responses. Zeb1 links the epithelial – mesenchymal transition and has been widely studied molecule in cancer biology. Except for the fact that it act as transcriptional repressor and represses IL2 gene promoter no other reports are available in immune biology, thereby rendering it a perfect candidate to be used for detailed characterization in dendritic cells. In our study, we found that Zeb1 depleted CD8α+DCs shows an increase in co-stimulatory marker like CD80 & CD86 whereas there is a decrease in MHC class I & II molecule. Thereafter at transcript & protein level we found decrease in pro-inflammatory & anti-inflammatory cytokine like IL6 & IL10 respectively, the bioactive form of IL12 i.e. IL12p70 which polarizes T cells towards Th1 response showed a significant decrease in bio-plex when compared with control CD8α+DCs. The regulatory markers which develop regulatory T cells like Pdl1, IL

Arctigenin functions as a selective agonist of estrogen receptor ? to restrict mTORC1 activation and consequent Th17 differentiation

OpenAIRE

Wu, Xin; Tong, Bei; Yang, Yan; Luo, Jinque; Yuan, Xusheng; Wei, Zhifeng; Yue, Mengfan; Xia, Yufeng; Dai, Yue

2016-01-01

Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ER? largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condit...

Intranasal delivery of cholera toxin induces th17-dominated T-cell response to bystander antigens.

Directory of Open Access Journals (Sweden)

Jee-Boong Lee

Full Text Available Cholera toxin (CT is a potent vaccine adjuvant, which promotes mucosal immunity to protein antigen given by nasal route. It has been suggested that CT promotes T helper type 2 (Th2 response and suppresses Th1 response. We here report the induction of Th17-dominated responses in mice by intranasal delivery of CT. This dramatic Th17-driving effect of CT, which was dependent on the B subunit, was observed even in Th1 or Th2-favored conditions of respiratory virus infection. These dominating Th17 responses resulted in the significant neutrophil accumulation in the lungs of mice given CT. Both in vitro and in vivo treatment of CT induced strongly augmented IL-6 production, and Th17-driving ability of CT was completely abolished in IL-6 knockout mice, indicating a role of this cytokine in the Th17-dominated T-cell responses by CT. These data demonstrate a novel Th17-driving activity of CT, and help understand the mechanisms of CT adjuvanticity to demarcate T helper responses.

The influence of leptin on Th1/Th2 balance in obese children with asthma

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Doaa Mohammed Youssef

2013-09-01

Full Text Available OBJECTIVE: In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes. METHODS: We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25 and non-obese (n = 25. From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied. RESULTS: Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV1 (% of predicted than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group. CONCLUSIONS: Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

International Nuclear Information System (INIS)

Yang, Xia; Qian, Feng; He, Hai-Yang; Liu, Kai-Jun; Lan, Yuan-Zhi; Ni, Bing; Tian, Yi; Fu, Xiao-Lan; Zhang, Ji; Shen, Zi-Gang; Li, Jian; Yin, Yi; Li, Jin-Tao; Wu, Yu-Zhang

2011-01-01

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4 + and CD8 + T cells, especially the CD4 + CD25 + Foxp3 + Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Energy Technology Data Exchange (ETDEWEB)

Yang, Xia [Institute of Immunology,Third Military Medical University, Chongqing (China); Qian, Feng [Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing (China); He, Hai-Yang; Liu, Kai-Jun [Institute of Immunology,Third Military Medical University, Chongqing (China); Lan, Yuan-Zhi [Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing (China); Ni, Bing; Tian, Yi; Fu, Xiao-Lan; Zhang, Ji; Shen, Zi-Gang; Li, Jian; Yin, Yi; Li, Jin-Tao; Wu, Yu-Zhang [Institute of Immunology,Third Military Medical University, Chongqing (China)

2011-12-02

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4{sup +} and CD8{sup +} T cells, especially the CD4{sup +}CD25{sup +}Foxp3{sup +} Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

The role of Th1 and Th17 cells in glomerulonephritis.

Science.gov (United States)

Azadegan-Dehkordi, Fatemeh; Bagheri, Nader; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

2015-04-01

T helper (Th) cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Directory of open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis.

Inflammasome and Fas-Mediated IL-1β Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo.

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Uchiyama, Ryosuke; Yonehara, Shin; Taniguchi, Shun'ichiro; Ishido, Satoshi; Ishii, Ken J; Tsutsui, Hiroko

2017-08-01

CD4 + Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN-γ and IL-17 double-producing CD4 + Th cells, termed Th17/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1β induces Th17/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes In the spleens of infected wild-type mice, Th17/Th1 cells were induced, and expressed T-bet and Rorγt. In Pycard -/- mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17/Th1 induction was abolished. In addition, the Fas-mediated IL-1β production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas -/- mice, whereas supplementation with recombinant IL-1β restored Th17/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas -/- mice infected with Listeria IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17/Th1 induction, indicating that IL-1β stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1β, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo. Copyright © 2017 by The American Association of Immunologists

Academic stress-induced changes in Th1- and Th2-cytokine response

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Areej M. Assaf

2017-12-01

Full Text Available Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8 and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10 on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

Academic stress-induced changes in Th1- and Th2-cytokine response.

Science.gov (United States)

Assaf, Areej M; Al-Abbassi, Reem; Al-Binni, Maysaa

2017-12-01

Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8) and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10) on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

Polarization converted coupler for plasma current drive experiments

International Nuclear Information System (INIS)

Arai, H.; Shimizu, S.; Goto, N.

1986-01-01

In this paper, the authors propose the polarization converted coupler which has narrow width shape and radiates electric field perpendicular to the main toroidal magnetic field. The advantages of the polarization converted coupler are as follows: (l) The rectangular waveguide as the transmission line has the high power capability. (2) The all metal design is not damaged by the fusion neutron. (3) The characteristic of this coupler is not changed widely, since the coupler has the matching section. For example, the VSWR of its input impedance is less than 2.0 for both water and air load. The authors present characteristics of the polarization converted coupler measured by the model experiments

Asymptotic behaviour in polarized and half-polarized U(1) symmetric vacuum spacetimes

International Nuclear Information System (INIS)

Isenberg, James; Moncrief, Vincent

2002-01-01

We use the Fuchsian algorithm to study the behaviour near the singularity of certain families of U(1) symmetric solutions of the vacuum Einstein equations (with the U(1) isometry group acting spatially). We consider an analytic family of polarized solutions with the maximum number of arbitrary functions consistent with the polarization condition (one of the 'gravitational degrees of freedom' is turned off) and show that all members of this family are asymptotically velocity term dominated (AVTD) as one approaches the singularity. We show that the same AVTD behaviour holds for a family of 'half-polarized' solutions, which is defined by adding one extra arbitrary function to those characterizing the polarized solutions. (The full set of nonpolarized solutions involves two extra arbitrary functions.) Using SL(2, R) Geroch transformations, we produce a further class of U(1) symmetric solutions with AVTD behaviour. We begin to address the issue of whether AVTD behaviour is independent of the choice of time foliation by showing that indeed AVTD behaviour is seen for a wide class of choices of harmonic time in the polarized and half-polarized (U(1) symmetric vacuum) solutions discussed here

Low-frequency current drive and helicity injection

International Nuclear Information System (INIS)

Chan, V.S.; Miller, R.L.; Ohkawa, T.

1990-01-01

For ω much-lt Ω i , where Ω i is the ion cyclotron frequency, circularly polarized waves can drive current far exceeding the current resulting from linearly polarized waves. Further, the efficiency can be independent of plasma density. In some cases, this circular polarization may be interpreted in terms of helicity injection. For tokamak applications, where the wavenumber in the toroidal direction is a real quantity, wave helicity is injected only with finite E z waves, where z is the direction of the static magnetic field. The Alfven waves are possible current drive candidates but, in the cylindrical model considered, the compressional wave is weakly damped because E z =0, while the shear Alfven wave is totally absorbed at the surface because of finite E z . A mixture of the two modes is shown to drive an oscillatory surface current even though the efficiency is high and independent of density. A more promising current drive candidate is a fast wave that propagates to the plasma interior and is damped by the minority cyclotron resonance. Near the minority mode conversion region, the fast wave is left-handed circularly polarized and it has a small but finite E z component at high electron temperatures. The current drive efficiency, although not as high as that of the Alfven wave, is still good and independent of density, making it attractive for fusion reactors

IL-34 and CSF-1 display an equivalent macrophage differentiation ability but a different polarization potential.

Science.gov (United States)

Boulakirba, Sonia; Pfeifer, Anja; Mhaidly, Rana; Obba, Sandrine; Goulard, Michael; Schmitt, Thomas; Chaintreuil, Paul; Calleja, Anne; Furstoss, Nathan; Orange, François; Lacas-Gervais, Sandra; Boyer, Laurent; Marchetti, Sandrine; Verhoeyen, Els; Luciano, Frederic; Robert, Guillaume; Auberger, Patrick; Jacquel, Arnaud

2018-01-10

CSF-1 and IL-34 share the CSF-1 receptor and no differences have been reported in the signaling pathways triggered by both ligands in human monocytes. IL-34 promotes the differentiation and survival of monocytes, macrophages and osteoclasts, as CSF-1 does. However, IL-34 binds other receptors, suggesting that differences exist in the effect of both cytokines. In the present study, we compared the differentiation and polarization abilities of human primary monocytes in response to CSF-1 or IL-34. CSF-1R engagement by one or the other ligands leads to AKT and caspase activation and autophagy induction through expression and activation of AMPK and ULK1. As no differences were detected on monocyte differentiation, we investigated the effect of CSF-1 and IL-34 on macrophage polarization into the M1 or M2 phenotype. We highlighted a striking increase in IL-10 and CCL17 secretion in M1 and M2 macrophages derived from IL-34 stimulated monocytes, respectively, compared to CSF-1 stimulated monocytes. Variations in the secretome induced by CSF-1 or IL-34 may account for their different ability to polarize naïve T cells into Th1 cells. In conclusion, our findings indicate that CSF-1 and IL-34 exhibit the same ability to induce human monocyte differentiation but may have a different ability to polarize macrophages.

Protease activity of Per a 10 potentiates Th2 polarization by increasing IL-23 and OX40L.

Science.gov (United States)

Agrawal, Komal; Kale, Sagar L; Arora, Naveen

2015-12-01

Proteases are implicated in exacerbation of allergic diseases. In this study, the role of proteolytic activity of Per a 10 was evaluated on Th2 polarization. Intranasal administration of Per a 10 in mice led to allergic airway inflammation as seen by higher IgE levels, cellular infiltration, IL-17A, and Th2 cytokines, whereas, inactive (Δ)Per a 10 showed attenuated response. There was an increased OX40L expression on lung and lymph node dendritic cells in Per a 10 immunized group and on Per a 10 stimulated BMDCs. Reduction in CD40 expression without any change at transcript level in lungs of Per a 10 immunized mice suggested CD40 cleavage. BMDCs pulsed with Per a 10 showed reduced CD40 expression with lower IL-12p70 secretion as compared to heat inactivated Per a 10. IL-23, TNF-α, and IL-6 levels were significantly higher in Per a 10 stimulated BMDCs supernatant. In DC-T cell coculture studies, Per a 10 pulsed BMDCs showed higher levels of IL-4 and IL-13 that were reduced on blocking of either IL-23 or OX40L. In conclusion, the data suggests a critical role of protease activity of Per a 10 in promoting Th2 polarization by increasing IL-23 secretion and OX40L expression on dendritic cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CD38 gene-modified dendritic cells inhibit murine asthma development by increasing IL-12 production and promoting Th1 cell differentiation.

Science.gov (United States)

Wang, Jiaoli; Zhu, Weiguo; Chen, Yinghu; Lin, Zhendong; Ma, Shenglin

2016-11-01

Predominant T helper (Th)2 and impaired Th1 cell polarization has a crucial role in the development of asthma. Cluster of differentiation (CD)38 is associated with the increased release of interleukin (IL)‑12 from dendritic cells (DCs) and DC‑induced Th1 cell polarization. However, whether CD38 expression affects DC function in asthma development remains unknown. In the current study, adenoviruses were constructed containing the murine CD38 gene. Overexpression of CD38 protein level in DCs induced from bone‑marrow derived DCs (BMDCs) by recombinant mouse granulocyte macrophage colony‑stimulating factor and IL‑4 was achieved through 24 h adenovirus infection. The results demonstrated that BMDCs with CD38 overexpression exhibited no phenotypic change; however, following stimulation with lipopolysaccharide (LPS), maturation and IL‑12 secretion were increased. In addition, CD38‑overexpressing BMDCs stimulated with LPS exhibited more effective Th1 cell differentiation. Mice that were administered CD38‑overexpressing BMDCs exhibited milder symptoms of asthma. Furthermore, decreased IL‑4, IL‑5 and IL‑13 levels were detected in bronchoalveolar lavage fluid (BALF), reduced immunoglobulin E levels were measured in the sera, and increased interferon‑γ was detected in BALF from the recipients of CD38‑overexpressing BMDCs. Increased phosphorylated‑p38 expression was also detected in LPS-stimulated CD38-overexpressing BMDCs, whereas pretreatment with a p38‑specific inhibitor was able to abolish the effects of LPS stimulation and CD38 overexpression on IL‑12 release and Th1 cell differentiation in BMDCs. These results suggested that CD38 may be involved in the DC function of alleviating asthma via restoration of the Th1/Th2 balance, thus providing a novel strategy for asthma therapy.

Role of Th1 and Th2 cells in autoimmune demyelinating disease

NARCIS (Netherlands)

Nagelkerken, L.

1998-01-01

Evidence is accumulating that Th1 cells play an important role in the development of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), whereas Th2 cells contribute to recovery from disease. A maj or determinant in the development of Th1 and Th2 cells is the type of

Design of a Fused-Silica Subwavelength Polarizing Beam Splitter Grating Based on the Modal Method

International Nuclear Information System (INIS)

Hua-Jun, Zhao; Dai-Rong, Yuan; Pei, Wang; Yong-Hua, Lu; Hai, Ming

2010-01-01

A polarizing beam splitter (PBS) design based on a fused-silica lamellar subwavelength transmission grating is demonstrated with the modal method, where TE- and TM-polarized waves are mainly diffracted in the −1 st and 0 th orders, respectively. The physical explanation of the grating diffraction is illustrated by the interference of the corresponding parts of the two propagating modes, which is very similar to a Mach–Zehnder interferometer. It is shown that diffraction efficients over 99% for a TM-polarized wave in the −1 st order and 90% for a TE-polarized wave in the 0 th order are obtained at the wavelength of 1.053 μm. The polarization transmission extinction ratios are better than 33 dB and 51 dB for the order 0 th and the −1 st order, respectively. The splitting properties of the PBS grating designed by the modal method are in good agreement with the results simulated by the rigorous coupled wave analysis method. (fundamental areas of phenomenology(including applications))

How It's Made - Polarized Proton Beam (444th Brookhaven Lecture)

International Nuclear Information System (INIS)

Zelenski, Anatoli

2008-01-01

Experiments with polarized beams at RHIC will provide fundamental tests of QCD, and the electro-weak interaction reveal the spin structure of the proton. Polarization asymmetries and parity violation are the strong signatures for identification of the fundamental processes, which are otherwise inaccessible. Such experiments require the maximum available luminosity and therefore polarization must be obtained as an extra beam quality without sacrificing intensity. There are proposals to polarize the high-energy proton beam in the storage rings by the Stern-Gerlach effect or spin-filter techniques. But so far, the only practically available option is acceleration of the polarized beam produced in the source and taking care of polarization survival during acceleration and storage. Two major innovations -- the 'Siberian Snake' technique for polarization preservation during acceleration and high current polarized proton sources make spin physics with the high-energy polarized beams feasible. The RHIC is the first high-energy collider, where the 'Siberian Snake' technique allowed of polarized proton beam acceleration up-to 250 GeV energy. The RHIC unique Optically Pumped Polarized Ion Source produces sufficient polarized beam intensity for complete saturation of the RHIC acceptance. This polarization technique is based on spin-transfer collisions between a proton or atomic hydrogen beam of a few keV beam energy and optically pumped alkali metal vapors. From the first proposal and feasibility studies to the operational source this development can be considered as example of successful unification of individual scientists ingenuity, international collaboration and modern technology application for creation of a new polarization technique, which allowed of two-to-three order of magnitude polarized beam intensity increase sufficient for loading the RHIC to its full capacity for polarization studies.

Alcohol mixed with energy drink use among u.s. 12th-grade students: prevalence, correlates, and associations with unsafe driving.

Science.gov (United States)

Martz, Meghan E; Patrick, Megan E; Schulenberg, John E

2015-05-01

The consumption of alcohol mixed with energy drinks (AmED) is a risky drinking behavior, most commonly studied using college samples. We know little about rates of AmED use and its associations with other risk behaviors, including unsafe driving, among high school students. This study examined the prevalence and correlates of AmED use among high school seniors in the United States. Nationally representative analytic samples included 6,498 12th-grade students who completed Monitoring the Future surveys in 2012 and 2013. Focal measures included AmED use, sociodemographic characteristics, academic and social factors, other substance use, and unsafe driving (i.e., tickets/warnings and accidents) after alcohol consumption. Approximately one in four students (24.8%) reported AmED use during the past 12 months. Rates of AmED use were highest among males and white students. Using multivariable logistic regression models controlling for sociodemographic characteristics, results indicate that students who cut class, spent more evenings out for fun and recreation, and reported binge drinking, marijuana use, and illicit drug use had a greater likelihood of AmED use. AmED use was also associated with greater odds of alcohol-related unsafe driving, even after controlling for sociodemographic, academic, and social factors and other substance use. AmED use among 12th-grade students is common and associated with certain sociodemographic, academic, social, and substance use factors. AmED use is also related to alcohol-related unsafe driving, which is a serious public health concern. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

SjCRT, a recombinant Schistosoma japonicum calreticulin, induces maturation of dendritic cells and a Th1-polarized immune response in mice

Directory of Open Access Journals (Sweden)

Lizhen Ma

2017-11-01

Full Text Available Abstract Background It is well known that immunization of radiation-attenuated (RA schistosoma cercariae or schistosomula can induce high levels of protective immunity against schistosoma cercariae reinfection in many animals. Many studies have shown that the Th1 cellular immune response is crucial for the protective effect elicited by RA schistosomula. However, the molecular mechanism of this strong protective immunity remains unclear. Methods The expression profiles of Schistosoma japonicum calreticulin (SjCRT in RA and normal schistosoma-derived cells were investigated by flow cytometry. The effect of recombinant SjCRT (rSjCRT on mouse dendritic cells (DCs was determined by FACS, ELISA and RT-PCR analysis. We also analyzed the effects of SjCRT on the activation of spleen cells from mice immunized with rSjCRT by detecting lymphocyte proliferation and the cytokine profiles of splenocytes. Results We found that the expression level of SjCRT in the cells from RA larvae was significantly higher than that in cells from normal schistosomula at early stages of development (day 4. The results of effect of rSjCRT on mouse DCs showed that rSjCRT could induce phenotypic and functional maturation of DCs, and SjCRT bound to the surface of DCs through the CD91 receptor and could be engulfed by DCs. The results of activation of splenocytes from mice immunized with rSjCRT also demonstrate that rSjCRT can effectively stimulate the proliferative response of splenic lymphocytes, elicit splenocytes from immunized mice to secrete high levels of IFN-γ, TNF-α and IL-4, and activate CD4+ T cells to produce high levels of IFN-γ. Conclusion SjCRT is one of the immunostimulatory molecules released from RA schistosomula cells, might play a crucial role in conferring a Th1-polarized immune response induced by RA cercariae/schistosomula in mice, and is a candidate molecule responsible for the high levels of protective immunity induced by RA schistosomula.

NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes.

Science.gov (United States)

Tellechea, Mónica; Buxadé, Maria; Tejedor, Sonia; Aramburu, Jose; López-Rodríguez, Cristina

2018-01-01

Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings. We found that both in classically and alternatively polarized macrophages, NFAT5 enhanced functions associated with a proinflammatory profile such as bactericidal capacity and the ability to promote Th1 polarization over Th2 responses. In this regard, NFAT5 upregulated the Th1-stimulatory cytokine IL-12 in classically activated macrophages, whereas in alternatively polarized ones it enhanced the expression of the pro-Th1 mediators Fizz-1 and arginase 1, indicating that it could promote proinflammatory readiness by regulating independent genes in differently polarized macrophages. Finally, adoptive transfer assays in vivo revealed a reduced antitumor capacity in NFAT5-deficient macrophages against syngeneic Lewis lung carcinoma and ID8 ovarian carcinoma cells, a defect that in the ID8 model was associated with a reduced accumulation of effector CD8 T cells at the tumor site. Altogether, detailed analysis of the effect of NFAT5 in pro- and anti-inflammatory macrophages uncovered its ability to regulate distinct genes under both polarization modes and revealed its predominant role in promoting proinflammatory macrophage functions. Copyright © 2017 by The American Association of Immunologists, Inc.

Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients.

Science.gov (United States)

Libetta, C; Rampino, T; Dal Canton, A

2001-08-01

T-helper (Th) lymphocytes consist of Th1 and Th2 subsets. Th1 cells are effectors of cell-mediated immunity and secrete interferon-gamma (IFN-gamma), which recruits new Th1 cells in cooperation with interleukin-12 (IL-12; produced by monocytes) and inhibits Th2 differentiation. Th2 cells produce IL-4 and IL-10, which inhibit IFN-gamma secretion and cell immunity. We investigated whether the impaired immune response in uremia is associated with an altered balance of Th1/Th2. Peripheral-blood mononuclear cells (PBMCs) were collected from patients with chronic renal failure (CRF) on conservative treatment (CRF patients), patients with end-stage renal disease (ESRD) on regular hemodialysis therapy (ESRD-HD patients), and healthy controls (CON). CD4(+) cells were isolated from PBMCs by negative selection using a magnetic labeling system. PBMCs and purified CD4(+) cells were cultured in Iscove's medium and Iscove's medium plus mitogens (phytohemagglutinin and lipopolysaccharide). IFN-gamma, IL-12, IL-4, and IL-10 were measured in supernatant. The constitutive release of IL-4 and IL-10 by PBMCs and CD4(+) cells of CRF and ESRD-HD patients was increased by five to eight times in comparison with CON (P CON, 115.8 pg/2 x10(6) cells; CRF, 81.8 pg/2 x10(6) cells; ESRD-HD, 9.3 pg/2 x10(6) cells; CD4(+) cells: CON, 358.0 pg/5 x 10(5) cells; CRF, 165.4 pg/5 x 10(5) cells; ESRD-HD, 43.5 pg/5 x 10(5) cells). The ability of PBMCs of ESRD-HD patients to secrete IFN-gamma was recovered after IL-4 and IL-10 neutralization. Uremia is associated with a prevalence of Th1 over Th2 cells and a configuration of cytokine network that depresses cell-mediated immunity.

Characterization of polarized THP-1 macrophages and polarizing ability of LPS and food compounds.

Science.gov (United States)

Chanput, Wasaporn; Mes, Jurriaan J; Savelkoul, Huub F J; Wichers, Harry J

2013-02-01

Little is known about the polarizing potential of currently used human macrophage cell lines, while a better understanding phenomena can support the prediction of effects in vivo based on in vitro analysis. To test the polarization capability of PMA differentiated-THP-1 macrophages (M0), cells were stimulated with 20 ng ml(-1) IFNγ + 1 μg ml(-1) LPS and 20 ng ml(-1) IL-4, which are known to influence macrophage polarization in vivo and ex vivo into the M1 and M2 state, respectively. Apart from several well-known M1 and M2 markers, also new possible markers for M1 and M2 polarization were analysed in this study. The expression of M1 marker genes was up-regulated in IFNγ + LPS stimulated-M0 THP-1 macrophages. The IL-4 stimulated-M0 THP-1 macrophages expressed M2 cell membrane receptor genes. However, M2 chemokine and their receptor genes were only slightly up-regulated which might be due to the complexity of the secondary cell-cell interaction of the chemokine system. Lipopolysaccharides from E. coli (LPS) and food compounds [lentinan, vitamin D3 (vD3) and the combination of lentinan + vitamin D3 (Len + vD3)] were investigated for their polarizing ability on M0 THP-1 macrophages towards either the M1 or M2 state. LPS (700 ng ml(-1)) was able to skew M0 THP-1 macrophages towards the M1 direction since all analysed M1 marker genes were strongly expressed. Lentinan, vD3 and Len + vD3 did not induce expression of either M1 or M2 markers, indicating no polarizing ability of these compounds. Based on the expression of M1 and M2 marker genes we concluded that THP-1 macrophages could be successfully polarized into either the M1 or M2 state. Therefore, they can be used as a new macrophage polarizing model to estimate the polarizing/switching ability of test food compounds.

Atherosclerosis-Driven Treg Plasticity Results in Formation of a Dysfunctional Subset of Plastic IFNγ+ Th1/Tregs.

Science.gov (United States)

Butcher, Matthew J; Filipowicz, Adam R; Waseem, Tayab C; McGary, Christopher M; Crow, Kevin J; Magilnick, Nathaniel; Boldin, Mark; Lundberg, Patric S; Galkina, Elena V

2016-11-11

Forkhead box P3 + T regulatory cells (Tregs) are key players in maintaining immune homeostasis. Evidence suggests that Tregs respond to environmental cues to permit or suppress inflammation. In atherosclerosis, Th1-driven inflammation affects Treg homeostasis, but the mechanisms governing this phenomenon are unclear. Here, we address whether atherosclerosis impacts Treg plasticity and functionality in Apoe - /- mice, and what effect Treg plasticity might have on the pathology of atherosclerosis. We demonstrate that atherosclerosis promotes Treg plasticity, resulting in the reduction of CXCR3 + Tregs and the accumulation of an intermediate Th1-like interferon (IFN)-γ + CCR5 + Treg subset (Th1/Tregs) within the aorta. Importantly, Th1/Tregs arise in atherosclerosis from bona fide Tregs, rather than from T-effector cells. We show that Th1/Tregs recovered from atherosclerotic mice are dysfunctional in suppression assays. Using an adoptive transfer system and plasticity-prone Mir146a -/- Tregs, we demonstrate that elevated IFNγ + Mir146a -/- Th1/Tregs are unable to adequately reduce atherosclerosis, arterial Th1, or macrophage content within Apoe -/- mice, in comparison to Mir146a +/+ Tregs. Finally, via single-cell RNA-sequencing and real-time -polymerase chain reaction, we show that Th1/Tregs possess a unique transcriptional phenotype characterized by coexpression of Treg and Th1 lineage genes and a downregulation of Treg-related genes, including Ikzf2, Ikzf4, Tigit, Lilrb4, and Il10. In addition, an ingenuity pathway analysis further implicates IFNγ, IFNα, interleukin-2, interleukin-7, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), T-cell receptor, and Csnk2b-related pathways in regulating Treg plasticity. Atherosclerosis drives Treg plasticity, resulting in the accumulation of dysfunctional IFNγ + Th1/Tregs that may permit further arterial inflammation and atherogenesis. © 2016 American Heart Association, Inc.

ThDof1.4 and ThZFP1 constitute a transcriptional regulatory cascade involved in salt or osmotic stress in Tamarix hispida.

Science.gov (United States)

Zang, Dandan; Wang, Lina; Zhang, Yiming; Zhao, Huimin; Wang, Yucheng

2017-07-01

Identification of the upstream regulators of a gene is important to characterize the transcriptional pathway and the function of the gene. Previously, we found that a zinc finger protein (ThZFP1) is involved in abiotic stress tolerance of Tamarix hispida. In the present study, we further investigated the transcriptional pathway of ThZFP1. Dof motifs are abundant in the ThZFP1 promoter; therefore, we used them to screen for transcriptional regulators of ThZFP1. A Dof protein, ThDof1.4, binds to the Dof motif specifically, and was hypothesized as the upstream regulator of ThZFP1. Further study showed that overexpression of ThDof1.4 in T. hispida activated the expression of GUS controlled by the ThZFP1 promoter. In T. hispida, transient overexpression of ThDof1.4 increased the transcripts of ThZFP1; conversely, transient RNAi-silencing of ThDof1.4 reduced the expression of ThZFP1. Chromatin immunoprecipitation indicated that ThDof1.4 binds to the ThZFP1 promoter. Additionally, ThDof1.4 and ThZFP1 share similar expression patterns in response to salt or drought stress. Furthermore, like ThZFP1, ThDof1.4 could increase the proline level and enhance ROS scavenging capability to improve salt and osmotic stress tolerance. Together, these results suggested that ThDof1.4 and ThZFP1 form a transcriptional regulatory cascade involved in abiotic stress resistance in T. hispida.

Down-regulation of the Th1, Th17, and Th22 pathways due to anti-TNF-α treatment in psoriasis.

Science.gov (United States)

Luan, Li; Han, Shixin; Wang, Hua; Liu, Xiaoming

2015-12-01

Psoriasis is a T-cell-mediated chronic inflammatory dermatosis. Th1, Th17 and Th22 cells are suggested to contribute to the pathogenesis of psoriasis. To determine whether treatment with the anti-tumor-necrosis-factor antagonist, adalimumab, induces significant modulation of the Th1, Th17 and Th22 pathways, and correlates cellular activity with clinical response. This study included 21 patients with moderate-to-severe psoriasis who were treated with adalimumab, and 10 healthy control subjects. Blood samples were collected at baseline and at week 12. Flow cytometry was used to analyze the frequency of circulating Th1, Th17 and Th22 cells. Real-time polymerase chain reaction was used to analyze the expression of T-bet (Th1-related), retinoid-acid receptor-related orphan receptor gamma t (RORγt, Th17-related) and aryl hydrocarbon receptor (AHR, Th22-related). An enzyme-linked immunosorbent assay was used to analyze the serum levels of IFN-γ, IL-17, IL-22, IL-6 and tumor necrosis factor-α (TNF-α). At baseline, the frequencies of Th1, Th17 and Th22 cells were higher in psoriasis patients compared to the healthy controls. The expression of transcription factors T-bet, RORγt and AHR, and the serum levels of IFN-γ, IL-17, IL-22, IL-6 and TNF-α were higher in psoriasis patients compared to the healthy controls. After adalimumab therapy, there was a significant decline in the frequencies of Th1, Th17 and Th22 cells, and a concomitant decrease in the levels of their associated transcription factors and cytokines. The results suggest that the anti-tumor-necrosis-factor antagonist, adalimumab, disrupts the Th1, Th17 and Th22 pathways, resulting in clinical improvement of psoriasis. Copyright © 2015 Elsevier B.V. All rights reserved.

H1 antihistamines and driving

OpenAIRE

Florin-Dan, Popescu

2008-01-01

Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion, Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and...

Modulation of chicken macrophage effector function by Th1/Th2 cytokines

Science.gov (United States)

Regulation of macrophage activity by TH1/2 cytokines is important to maintain the balance of immunity to provide adequate protective immunity while avoiding excessive inflammation. IFN-gamma and IL-4 are the hallmark TH1 and TH2 cytokines, respectively. In avian species, information concerning reg...

Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria.

Science.gov (United States)

Lönnberg, Tapio; Svensson, Valentine; James, Kylie R; Fernandez-Ruiz, Daniel; Sebina, Ismail; Montandon, Ruddy; Soon, Megan S F; Fogg, Lily G; Nair, Arya Sheela; Liligeto, Urijah; Stubbington, Michael J T; Ly, Lam-Ha; Bagger, Frederik Otzen; Zwiessele, Max; Lawrence, Neil D; Souza-Fonseca-Guimaraes, Fernando; Bunn, Patrick T; Engwerda, Christian R; Heath, William R; Billker, Oliver; Stegle, Oliver; Haque, Ashraful; Teichmann, Sarah A

2017-03-03

Differentiation of naïve CD4 + T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo . By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice. By tracking clonality using endogenous TCR sequences, we first demonstrated that Th1/Tfh bifurcation had occurred at both population and single-clone levels. Next, we identified genes whose expression was associated with Th1 or Tfh fates, and demonstrated a T-cell intrinsic role for Galectin-1 in supporting a Th1 differentiation. We also revealed the close molecular relationship between Th1 and IL-10-producing Tr1 cells in this infection. Th1 and Tfh fates emerged from a highly proliferative precursor that upregulated aerobic glycolysis and accelerated cell cycling as cytokine expression began. Dynamic gene expression of chemokine receptors around bifurcation predicted roles for cell-cell in driving Th1/Tfh fates. In particular, we found that precursor Th cells were coached towards a Th1 but not a Tfh fate by inflammatory monocytes. Thus, by integrating genomic and computational approaches, our study has provided two unique resources, a database www.PlasmoTH.org, which facilitates discovery of novel factors controlling Th1/Tfh fate commitment, and more generally, GPfates, a modelling framework for characterizing cell differentiation towards multiple fates.

Continuous wave protocol for simultaneous polarization and optical detection of P1-center electron spin resonance

Science.gov (United States)

Kamp, E. J.; Carvajal, B.; Samarth, N.

2018-01-01

The ready optical detection and manipulation of bright nitrogen vacancy center spins in diamond plays a key role in contemporary quantum information science and quantum metrology. Other optically dark defects such as substitutional nitrogen atoms (`P1 centers') could also become potentially useful in this context if they could be as easily optically detected and manipulated. We develop a relatively straightforward continuous wave protocol that takes advantage of the dipolar coupling between nitrogen vacancy and P1 centers in type 1b diamond to detect and polarize the dark P1 spins. By combining mutual spin flip transitions with radio frequency driving, we demonstrate the simultaneous optical polarization and detection of the electron spin resonance of the P1 center. This technique should be applicable to detecting and manipulating a broad range of dark spin populations that couple to the nitrogen vacancy center via dipolar fields, allowing for quantum metrology using these spin populations.

The effect of laser spot shapes on polar-direct-drive implosions on the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Weilacher, F.; Radha, P. B., E-mail: rbah@lle.rochester.edu; Collins, T. J. B.; Marozas, J. A. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States)

2015-03-15

Ongoing polar-direct-drive (PDD) implosions on the National Ignition Facility (NIF) [J. D. Lindl and E. I. Moses, Phys. Plasmas 18, 050901 (2011)] use existing NIF hardware, including indirect-drive phase plates. This limits the performance achievable in these implosions. Spot shapes are identified that significantly improve the uniformity of PDD NIF implosions; outer surface deviation is reduced by a factor of 7 at the end of the laser pulse and hot-spot distortion is reduced by a factor of 2 when the shell has converged by a factor of ∼10. As a result, the neutron yield increases by approximately a factor of 2. This set of laser spot shapes is a combination of circular and elliptical spots, along with elliptical spot shapes modulated by an additional higher-intensity ellipse offset from the center of the beam. This combination is motivated in this paper. It is also found that this improved implosion uniformity is obtained independent of the heat conduction model. This work indicates that significant improvement in performance can be obtained robustly with the proposed spot shapes.

The effect of laser spot shapes on polar-direct-drive implosions on the National Ignition Facility

International Nuclear Information System (INIS)

Weilacher, F.; Radha, P. B.; Collins, T. J. B.; Marozas, J. A.

2015-01-01

Ongoing polar-direct-drive (PDD) implosions on the National Ignition Facility (NIF) [J. D. Lindl and E. I. Moses, Phys. Plasmas 18, 050901 (2011)] use existing NIF hardware, including indirect-drive phase plates. This limits the performance achievable in these implosions. Spot shapes are identified that significantly improve the uniformity of PDD NIF implosions; outer surface deviation is reduced by a factor of 7 at the end of the laser pulse and hot-spot distortion is reduced by a factor of 2 when the shell has converged by a factor of ∼10. As a result, the neutron yield increases by approximately a factor of 2. This set of laser spot shapes is a combination of circular and elliptical spots, along with elliptical spot shapes modulated by an additional higher-intensity ellipse offset from the center of the beam. This combination is motivated in this paper. It is also found that this improved implosion uniformity is obtained independent of the heat conduction model. This work indicates that significant improvement in performance can be obtained robustly with the proposed spot shapes

Human B cells induce dendritic cell maturation and favour Th2 polarization by inducing OX-40 ligand

Science.gov (United States)

Maddur, Mohan S.; Sharma, Meenu; Hegde, Pushpa; Stephen-Victor, Emmanuel; Pulendran, Bali; Kaveri, Srini V.; Bayry, Jagadeesh

2015-01-01

Dendritic cells (DCs) play a critical role in immune homeostasis by regulating the functions of various immune cells, including T and B cells. Notably, DCs also undergo education on reciprocal signalling by these immune cells and environmental factors. Various reports demonstrated that B cells have profound regulatory functions, although only few reports have explored the regulation of human DCs by B cells. Here we demonstrate that activated but not resting B cells induce maturation of DCs with distinct features to polarize Th2 cells that secrete interleukin (IL)-5, IL-4 and IL-13. B-cell-induced maturation of DCs is contact dependent and implicates signalling of B-cell activation molecules CD69, B-cell-activating factor receptor, and transmembrane activator and calcium-modulating cyclophilin ligand interactor. Mechanistically, differentiation of Th2 cells by B-cell-matured DCs is dependent on OX-40 ligand. Collectively, our results suggest that B cells have the ability to control their own effector functions by enhancing the ability of human DCs to mediate Th2 differentiation. PMID:24910129

Regulation of nasal airway homeostasis and inflammation in mice by SHP-1 and Th2/Th1 signaling pathways.

Directory of Open Access Journals (Sweden)

Seok Hyun Cho

Full Text Available Allergic rhinitis is a chronic inflammatory disease orchestrated by Th2 lymphocytes. Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1 is known to be a negative regulator in the IL-4α/STAT-6 signaling pathway of the lung. However, the role of SHP-1 enzyme and its functional relationship with Th2 and Th1 cytokines are not known in the nasal airway. In this study, we aimed to study the nasal inflammation as a result of SHP-1 deficiency in viable motheaten (mev mice and to investigate the molecular mechanisms involved. Cytology, histology, and expression of cytokines and chemokines were analyzed to define the nature of the nasal inflammation. Targeted gene depletion of Th1 (IFN-γ and Th2 (IL-4 and IL-13 cytokines was used to identify the critical pathways involved. Matrix metalloproteinases (MMPs were studied to demonstrate the clearance mechanism of recruited inflammatory cells into the nasal airway. We showed here that mev mice had a spontaneous allergic rhinitis-like inflammation with eosinophilia, mucus metaplasia, up-regulation of Th2 cytokines (IL-4 and IL-13, chemokines (eotaxin, and MMPs. All of these inflammatory mediators were clearly counter-regulated by Th2 and Th1 cytokines. Deletion of IFN-γ gene induced a strong Th2-skewed inflammation with transepithelial migration of the inflammatory cells. These findings suggest that SHP-1 enzyme and Th2/Th1 paradigm may play a critical role in the maintenance of nasal immune homeostasis and in the regulation of allergic rhinitis.

Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

Science.gov (United States)

Carvalho, Agostinho; Giovannini, Gloria; De Luca, Antonella; D'Angelo, Carmen; Casagrande, Andrea; Iannitti, Rossana G; Ricci, Giovanni; Cunha, Cristina; Romani, Luigina

2012-01-01

The recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling. PMID:22543832

Oxidative stress modulates the cytokine response of differentiated Th17 and Th1 cells.

Science.gov (United States)

Abimannan, Thiruvaimozhi; Peroumal, Doureradjou; Parida, Jyoti R; Barik, Prakash K; Padhan, Prasanta; Devadas, Satish

2016-10-01

Reactive oxygen species (ROS) signaling is critical in T helper (Th) cell differentiation; however its role in differentiated Th cell functions is unclear. In this study, we investigated the role of oxidative stress on the effector functions of in vitro differentiated mouse Th17 and Th1 cells or CD4 + T cells from patients with Rheumatoid Arthritis using pro-oxidants plumbagin (PB) and hydrogen peroxide. We found that in mouse Th cells, non-toxic concentration of pro-oxidants inhibited reactivation induced expression of IL-17A in Th17 and IFN-γ in Th1 cells by reducing the expression of their respective TFs, RORγt and T-bet. Interestingly, in both the subsets, PB increased the expression of IL-4 by enhancing reactivation induced ERK1/2 phosphorylation. We further investigated the cytokine modulatory effect of PB on CD4 + T cells isolated from PBMCs of patients with Rheumatoid Arthritis, a well-known Th17 and or Th1 mediated disease. In human CD4 + T cells from Rheumatoid Arthritis patients, PB reduced the frequencies of IL-17A + (Th17), IFN - γ + (Th1) and IL-17A + /IFN - γ + (Th17/1) cells and also inhibited the production of pro-inflammatory cytokines TNF-α and IL-6. N-Acetyl Cysteine (NAC) an antioxidant completely reversed PB mediated cytokine modulatory effects in both mouse and human cells indicating a direct role for ROS. Together our data suggest that oxidative microenvironment can alter cytokine response of terminally differentiated cells and thus altering intracellular ROS could be a potential way to target Th17 and Th1 cells in autoimmune disorders. Copyright © 2016. Published by Elsevier Inc.

Polarized target as analyzer of polarization of particle beam with spin Ssub(B)=1/2

International Nuclear Information System (INIS)

Golovin, V.M.; Golubeva, M.B.; Gornushkin, Yu.A.

1982-01-01

A possibility of using a polarized target as a target analyzer of beam particle polarization (Ssub(T)=1/2 Psub(T) vector) so that all the components of beam polarization Ssub(B)=1/2 anti Psub(B) should be determined in one experiment, is revealed. A proton polarization target is considered as a polarization target-analyzer. Asub(SK) and Asub(kk) asymmetry tensors are considered for elastic pp and pn scatterings by amplitudes of NN scattering which attain the values of 0.3-0.9 at 95-400 MeV. Asub(kk)(pp) and Asub(sk)(pp) are experimentally measured in the 445-576 MeV range. It is found that their highest absolute values are equal to 0.4-0.5 and 0.2-0.3 respectively. Elastic proton scattering on polarized electrons may be another variant of using polarized target for measuring proton beam polarization. Asub(sk) and Asub(kk) components of asymmetry tensor of elastic pe scattering are graphically presented. A possibility of using a polarized charge with spin I=1/2 as a target-analyzer of particle beam polarization is marked

Mycobacterium tuberculosis Latent Antigen Rv2029c from the Multistage DNA Vaccine A39 Drives TH1 Responses via TLR-mediated Macrophage Activation

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Haibo Su

2017-11-01

Full Text Available Targeting of Mycobacterium tuberculosis (MTB latent antigens comprises a crucial strategy for the development of alternative tuberculosis (TB vaccine(s that protects against TB reactivation. Here, we generated a multistage DNA vaccine, A39, containing the early antigens Ag85A and Rv3425 as well as the latency-associated protein Rv2029c, which conferred protective immunity in a pre-exposure mouse model. Moreover, administration of the A39 vaccination after MTB exposure inhibited reactivation and resulted in significantly lower bacterial loads in the lungs and spleen of mice, compared to those in the control population. Subsequently, we investigated the effect of Rv2029c on innate immunity and characterized the molecular details of the interaction of this protein with the host via iTRAQ proteomic and biochemical assay analyses. Rv2029c activated macrophages, triggered the production of pro-inflammatory cytokines, and promoted toll-like receptor/mitogen-activated protein kinase (TLR/MAPK-dependent macrophage apoptosis. Furthermore, Rv2029c treatment enhanced the ability of Mycobacterium bovis Bacillus Calmette-Guérin (BCG-infected macrophages to present antigens to CD4+ T cells in vitro, which correlated with an increase in MHC-II expression. Lastly, Rv2029c-treated macrophages activated T cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and IL-2, and specifically expanded a population of CD44highCD62LlowCD4+/CD8+ effector/memory cells, indicating that Rv2029c, as a specific recall antigen, contributes to Th1 polarization in T cell immunity. These results suggest that Rv2029c and A39 comprise promising targets for the development of next-generation clinical TB therapeutic vaccines.

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles.

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Guimarães, Poliana Macedo; Scavuzzi, Bruna Miglioranza; Stadtlober, Nicole Perugini; Franchi Santos, Lorena Flor da Rosa; Lozovoy, Marcell Alysson Batisti; Iriyoda, Tatiana Mayumi Veiga; Costa, Neide Tomimura; Reiche, Edna Maria Vissoci; Maes, Michael; Dichi, Isaias; Simão, Andréa Name Colado

2017-10-01

The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL- 4, IL-6, IL-10, IL-12 and IL-17 were measured and cytokines profiles were computed. IL-6, IL-12, IL-17, IFN-γ and IL-10 levels were significantly higher in SLE, while IL-4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL-6+IL-1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL-10 (positively associated) and IL-4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL-10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL-17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL-4 and IFNγ values. 25-OH vitamin D was inversely associated with IFN-γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.

The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice.

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Li, Xia; Wang, Bin; Li, Yuzhu; Wang, Li; Zhao, Xiangzhong; Zhou, Xianbin; Guo, Yuqi; Jiang, Guosheng; Yao, Chengfang

2013-01-09

The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and participates in RU486-induced abortion. Excessive uterine bleeding is the most common side effect of RU486-induced abortion; however, its etiopathogenesis has not been fully understood. Therefore, elucidating the correlation between the Th1/Th2/Th17/Treg paradigm and the volume of uterine bleeding may offer novel therapeutic target for reducing uterine bleeding in RU486-induced abortion. Leonurus sibiricus has been used in clinics to reduce postpartum hemorrhage with low toxicity and high efficiency; however, the effective constituents and therapeutic mechanism have not been described. Stachydrine hydrochloride is the main constituent of L. sibiricus, therefore L. sibiricus is regarded as a candidate for reducing uterine bleeding in RU486-induced abortion mice by regulating the Th1/Th2/Th17/Treg paradigm. The purpose of this study was to determine the Th1/Th2/Th17/Treg paradigm in uterine bleeding of RU486-induced abortion mice and to elucidate the immunopharmacologic effects of stachydrine hydrochloride on inducing the Th1/Th2/Th17/Treg paradigm in reducing the uterine bleeding volume in RU486-induced abortion mice. To investigate the Th1/Th2/Th17/Treg paradigm in uterine bleeding during RU486-induced abortion mice, pregnant BALB/c mice were treated with high- and low-dose RU486 (1.5mg/kg and 0.9 mg/kg, respectively), and the serum progesterone (P(4)) protein level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells in mice at the maternal-fetal interface were detected by ELISA assay, alkaline hematin photometric assay, and flow cytometry, respectively. To determine the regulatory effect of stachydrine hydrochloride on the Th1/Th2/Th17/Treg paradigm in vitro, splenocytes of non-pregnant mice were separated and treated with P(4,) RU486, and/or stachydrine hydrochloride (10(-5)M, 10(-4)M, and 10(-3)M, respectively). The proportions of Th1/Th2/Th17

Introduction to the special issue on the joint meeting of the 19th IEEE International Symposium on the Applications of Ferroelectrics and the 10th European Conference on the Applications of Polar Dielectrics.

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Tsurumi, Takaaki

2011-09-01

The joint meeting of the 19th IEEE International Symposium on the Applications of Ferroelectrics and the 10th European Conference on the Applications of Polar Dielectrics took place in Edinburgh from August 9-12, 2010. The conference was attended by 390 delegates from more than 40 different countries. There were 4 plenary speakers, 56 invited speakers, and a further 222 contributed oral presentations in 7 parallel session. In addition there were 215 poster presentations. Key topics addressed at the conference included piezoelectric materials, leadfree piezoelectrics, and multiferroics.

Effects of γ-rays on Th1 and Th2 immune function of mice

International Nuclear Information System (INIS)

Jin Wei; Cui Yufang; An Xiaoxia; Xu Han; Dong Bo; Liu Xiaolan; Luo Qingliang

2007-01-01

Objective: To observe the effects of 6 Gy whole body γ-irradiation on immune function of Th1 and Th2 in mouse, and to investigate the cellular and molecular mechanism of immune system injury induced by irradiation. Methods: Surface marker and intracellular cytokines of lymphocytes were stained with fluorescence-labeled monoclonal antibodies, then the changes of lymphocyte subpopulations, especially the Th1 and Th2 in mouse peripheral blood and spleen were analyzed by flow cytometry. Results: (1) 1 d after 6 Gy y- irradiation, lymphocytic subsets of CD 19 + and CD 8 + in spleen decreased apparently and the percentages of them were only 30% and 41% of control groups respectively (P 19 + and 14 d for CD 8 + respectively, however, up to 21 d post-irradiation they still did not return to control level. (2) Th1 subpopulations in mouse peripheral blood and spleen were significantly reduced at 1 d after irradiation and were only 2.6% and 7.6% of control groups (P 4 + / CD 8 + were significantly increased at 1 d post-irradiation in mouse spleen because of swift reduction of CD 8 + cells. Interestingly, either in peripheral blood or in spleen in irradiated mice, the ratio of Th1/Th2 were evidently raised because of the decrement of Th1 cells, exhibited obviously a phenomenon of predominant immune response of Th2 cells. Conclusions: It is suggested that the depression of mouse immune function induced by 6 Gy γ-irradiation might be caused by changes of CD 4 + /CD 8 + ratio, especially the imbalance of Th1/Th2 function subpopulations. It is shown that the imbalance of Th1/Th2 function subpopulations plays an important role in radiation-induced immune injury, thus providing a better insight into the molecular mechanism and new strategies for prevent and treatment measures of immune injury by irradiation. (authors)

Inducing elliptically polarized high-order harmonics from aligned molecules with linearly polarized femtosecond pulses

DEFF Research Database (Denmark)

Etches, Adam; Madsen, Christian Bruun; Madsen, Lars Bojer

2010-01-01

A recent paper reported elliptically polarized high-order harmonics from aligned N2 using a linearly polarized driving field [X. Zhou et al., Phys. Rev. Lett. 102, 073902 (2009)]. This observation cannot be explained in the standard treatment of the Lewenstein model and has been ascribed to many...

mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1/TH17/Treg Profile.

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Shurong Hu

Full Text Available It has been established that mammalian target of Rapamycin (mTOR inhibitors have anti-inflammatory effects in models of experimental colitis. However, the underlying mechanism is largely unknown. In this research, we investigate the anti-inflammatory effects of AZD8055, a potent mTOR inhibitor, on T cell response in dextran sulfate sodium (DSS-induced colitis in mice, a commonly used animal model of inflammatory bowel diseases (IBD. Severity of colitis is evaluated by changing of body weight, bloody stool, fecal consistency, histology evaluation and cytokine expression. We find that AZD8055 treatment attenuates DSS-induced body weight loss, colon length shortening and pathological damage of the colon. And AZD8055 treatment decreases colonic expression of genes encoding the pro-inflammatory cytokines interferon-γ, interleukin (IL-17A, IL-1β,IL-6 and tumor necrosis factor(TNF-a and increases colonic expression of anti-inflammatory cytokines IL-10. We show that AZD8055 treatment decreases the percentages of CD4+ T cells and CD8+ T cells in spleen, lymph nodes and peripheral blood of mice. We also find that AZD8055 treatment significantly reduces the number of T helper 1(TH1 cells and TH17 cells and increases regulatory T (Treg cells in the lamina propria and mesenteric lymph nodes. Furthermore, we demonstrates that AZD8055 suppresses the proliferation of CD4+ and CD8+ T cells and the differentiation of TH1/TH17 cells and expands Treg cells in vitro. The results suggest that, in experimental colitis, AZD8055 exerts anti-inflammatory effect by regulating T helper cell polarization and proliferation.

Th-1, Th-2 Cytokines Profile among Madurella mycetomatis Eumycetoma Patients.

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Nasr, Amre; Abushouk, Amir; Hamza, Anhar; Siddig, Emmanuel; Fahal, Ahmed H

2016-07-01

Eumycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by certain fungi, the most common being Madurella mycetomatis. The host defence mechanisms against fungi usually range from an early non-specific immune response to activation and induction of specific adaptive immune responses by the production of Th-1 and Th-2 cytokines. The aim of this study is to determine the levels of Th-1 and Th-2 cytokines in patients infected with Madurella mycetomatis, and the association between their levels and disease prognosis. This is a descriptive cross-sectional study conducted at the Mycetoma Research Centre, University of Khartoum, Sudan, where 70 patients with confirmed M. mycetomatis eumycetoma were enrolled; 35 with, and 35 without surgical excision. 70 healthy individuals from mycetoma endemic areas were selected as controls. The levels of serum cytokines were determined by cytometric bead array technique. Significantly higher levels of the Th-1 cytokines (IFN-γ, TNF-α, IL-1β and IL-2) were recorded in patients treated with surgical excision, compared to those treated without surgical excision. In contrast, the Th-2 cytokines (IL-4, IL-5, IL-6 and IL-10) were significantly lower in patients treated with surgical excision compared to those treated without surgical excision. In conclusion, the results of this study suggest that cell-mediated immunity can have a role to play in the pathogenesis of eumycetoma.

[A retrospective analysis of 97 drunk driving cases].

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Cheng, Xiang-Wei; Chu, Yun; Zong, Xiong-Xin; Wang, Zi-Wei; Chu, Jian-Xin

2013-04-01

Based on a retrospective analysis of the drunk driving cases, to explore the drunk drivers' personnel composition, occurrence time and psychology. As a result of punishment of the drunk driving by criminal law for one year from May 1st, 2011 to April 30th, 2012, 91 drunk driving cases were statistically analyzed the easy-happening time of drunk driving, the drunk drivers' age, gender, occupational characteristics, domicile and psychological factors. In 97 drunk driving cases, 26-40 years old, non-local domiciled and non-professional male drivers were prone to drunk driving at night from 22:00 to 5:00. The behavior of drunk driving is relevant to time, age, genders and occupation. The psychological characteristics of most drivers are fluky, making-life-easy, competitive and peacockish.

Magnetic correlations in UPt3 and U/sub 1-x/Th/sub x/Pt3

International Nuclear Information System (INIS)

Aeppli, G.; Bucher, E.; Goldman, A.I.; Shirane, G.; Broholm, C.; Kjems, J.K.

1988-01-01

Neutron scattering experiments on UPt 3 and U/sub 1-x/Th/sub x/Pt 3 are reviewed. At relatively high energies (/approximately/5 MeV), the magnetic fluctuation spectrum is modulated by the structure factor derived from short-range antiferromagnetic correlations where the two U ions in each unit cell are oppositely polarized. In contrast, at low energies (≤ 1 MeV), the diffuse inelastic scattering is associated with antiferromagnetic correlations where the unit cell is doubled. Nominally pure UPt 3 exhibits magnetic order with the wavevector corresponding to this doubling and a static moment of 0.02 +- 0.01 μ/sub B/. (U/sub 1-x/Th/sub x/)Pt 3 with x ≅ 0.05 exhibits ordering of the same type, but with a much larger static moment, 0.65 +- 0.1 μ/sub B/. Neutron scattering measurements on UPt 3 with implications for superconductivity are surveyed. 23 refs., 7 figs

Human Blood CD1c+ Dendritic Cells Promote Th1 and Th17 Effector Function in Memory CD4+ T Cells.

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Leal Rojas, Ingrid M; Mok, Wai-Hong; Pearson, Frances E; Minoda, Yoshihito; Kenna, Tony J; Barnard, Ross T; Radford, Kristen J

2017-01-01

Dendritic cells (DC) initiate the differentiation of CD4 + helper T cells into effector cells including Th1 and Th17 responses that play an important role in inflammation and autoimmune disease pathogenesis. In mice, Th1 and Th17 responses are regulated by different conventional (c) DC subsets, with cDC1 being the main producers of IL-12p70 and inducers of Th1 responses, while cDC2 produce IL-23 to promote Th17 responses. The role that human DC subsets play in memory CD4 + T cell activation is not known. This study investigated production of Th1 promoting cytokine IL-12p70, and Th17 promoting cytokines, IL-1β, IL-6, and IL-23, by human blood monocytes, CD1c + DC, CD141 + DC, and plasmacytoid DC and examined their ability to induce Th1 and Th17 responses in memory CD4 + T cells. Human CD1c + DC produced IL-12p70, IL-1β, IL-6, and IL-23 in response to R848 combined with LPS or poly I:C. CD141 + DC were also capable of producing IL-12p70 and IL-23 but were not as proficient as CD1c + DC. Activated CD1c + DC were endowed with the capacity to promote both Th1 and Th17 effector function in memory CD4 + T cells, characterized by high production of interferon-γ, IL-17A, IL-17F, IL-21, and IL-22. These findings support a role for CD1c + DC in autoimmune inflammation where Th1/Th17 responses play an important role in disease pathogenesis.

Down-regulation of Notch signaling pathway reverses the Th1/Th2 imbalance in tuberculosis patients.

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Li, Qifeng; Zhang, Hui; Yu, Liang; Wu, Chao; Luo, Xinhui; Sun, He; Ding, Jianbing

2018-01-01

Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the mechanisms for Th1/Th2 imbalance are still not well determined. Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Here, we used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively. Then, the Th1/Th2 ratios were determined by flow cytometry, and cytokines of IFN-γ, IL-4, IL-10 in the culture supernatant were measured by CBA method. The Notch signal pathway associated proteins Hes1, GATA3 and T-bet were quantitated by real-time PCR or immunoblotting. Our results showed that DAPT effectively inhibited the protein level of Hes1. In TB patients, the Th2 ratio increased in the PBMCs, alone with the high expression of GATA3 and IL-4, resulting in the high ratios of Th2/Th1 and GATA3/T-bet in TB patients. However, Th2 cells ratio decreased after blocking the Notch signaling pathway by DAPT and the Th2/Th1 ratio in TB patients were DAPT dose-dependent, accompanied by the decrease of IL-4 and GATA3. But, its influence on Th1 ratio and Th1 related T-bet and IFN-γ levels were not significant. In conclusion, our results suggest that blocking Notch signaling by DAPT could inhibit Th2 responses and restore Th1/Th2 imbalance in TB patients. Copyright © 2017. Published by Elsevier B.V.

Radiation-induced decrease of CD8+ dendritic cells contributes to Th1/Th2 shift.

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Liu, Hu; Li, Bailong; Jia, Xiaojing; Ma, Yan; Gu, Yifeng; Zhang, Pei; Wei, Qun; Cai, Jianming; Cui, Jianguo; Gao, Fu; Yang, Yanyong

2017-05-01

Exposure to ionizing radiation (IR) often reduce the helper T (Th) 1 like function, resulting in a Th1/Th2 imbalance, which could affect the efficacy of cancer radiotherapy. As the most potent antigen presenting cells, dendritic cells (DC) can be divided into several subsets with specialized function. However, there is no literature covering the changes of DC subsets and their roles in immune regulation in response to IR. In the present study, we were aimed to investigate the changes of DC subsets after IR and its relationship with Th1/Th2 immunity. We found a significant decrease of BDCA3+DC in the blood of patients treated with radiotherapy. CD8+DC, a mouse equivalent of human BDCA3+DC, was also found decreased in mice spleen, peripheral blood and lymph node tissues after irradiation. As CD8+DC mainly induce Th1 immunity, we tested the changes of Th1/Th2 response and found that IR caused a repression of Th1 immunity, indicating a possible role of CD8+DC in radiation-induced Th1/Th2 imbalance. We also found that a CD8+DC-inducing cytokine, Fms-like tyrosine kinase 3 ligand (FLT3 ligand), restored CD8+DC and reversed Th1/Th2 shift. And then we found that bone marrow cells from irradiated mice differentiated into less CD8+DC, which was also protected by FLT3 ligand. In conclusion, our data showed that IR induced a decrease of CD8+DC and Th1/Th2 shift, which was reversed by Flt3 ligand treatment, suggesting a novel mechanism for radiation-induced immunosuppression. Copyright © 2017. Published by Elsevier B.V.

The translational repressor T-cell intracellular antigen-1 (TIA-1) is a key modulator of Th2 and Th17 responses driving pulmonary inflammation induced by exposure to house dust mite.

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Simarro, Maria; Giannattasio, Giorgio; Xing, Wei; Lundequist, Emma-Maria; Stewart, Samantha; Stevens, Richard L; Orduña, Antonio; Boyce, Joshua A; Anderson, Paul J

2012-08-30

T-cell intracellular antigen-1 (TIA-1) is a translational repressor that dampens the production of proinflammatory cytokines and enzymes. In this study we investigated the role of TIA-1 in a mouse model of pulmonary inflammation induced by exposure to the allergenic extract (Df) of the house dust mite Dermatophagoides farinae. When intranasally challenged with a low dose of Df, mice lacking TIA-1 protein (Tia-1(-/-)) showed more severe airway and tissue eosinophilia, infiltration of lung bronchovascular bundles, and goblet cell metaplasia than wild-type littermates. Tia-1(-/-) mice also had higher levels of Df-specific IgE and IgG(1) in serum and ex vivo restimulated Tia-1(-/-) lymph node cells and splenocytes transcribed and released more Th2/Th17 cytokines. To evaluate the site of action of TIA-1, we studied the response to Df in bone marrow chimeras. These experiments revealed that TIA-1 acts on both hematopoietic and non-hematopoietic cells to dampen pulmonary inflammation. Our results identify TIA-1 as a negative regulator of allergen-mediated pulmonary inflammation in vivo. Thus, TIA-1 might be an important player in the pathogenesis of bronchial asthma. Copyright © 2012 Elsevier B.V. All rights reserved.

Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment

International Nuclear Information System (INIS)

Mori, Kazumasa; Haraguchi, Shigeki; Hiori, Miki; Shimada, Jun; Ohmori, Yoshihiro

2015-01-01

Tumor-associated macrophages (TAMs) are implicated in the growth, invasion and metastasis of various solid tumors. However, the phenotype of TAMs in premalignant lesions of solid tumors has not been clarified. In the present study, we identify the phenotype of TAMs in leukoplakia, an oral premalignant lesion, by immunohistochemical analysis and investigate the involvement of infiltrated T cells that participate in the polarization of TAMs. The subjects included 30 patients with oral leukoplakia and 10 individuals with normal mucosa. Hematoxylin and eosin slides were examined for the histological grades, and immunohistochemical analysis was carried out using antibodies against CD68 (pan-MΦ), CD80 (M1 MΦ), CD163 (M2 MΦ), CD4 (helper T cells: Th), CD8 (cytotoxic T cells), CXCR3, CCR5 (Th1), CCR4 (Th2), signal transducer and activator of transcription (STAT1), phosphorylated STAT1 (pSTAT1) and chemokine CXCL9. The differences in the numbers of positively stained cells among the different histological grades were tested for statistical significance using the Kruskal-Wallis test. Correlations between different types of immune cells were determined using Spearman’s rank analysis. An increase in the rate of CD163 + TAM infiltration was observed in mild and moderate epithelial dysplasia, which positively correlated with the rate of intraepithelial CD4 + Th cell infiltration. Although CCR4 + cells rarely infiltrated, CXCR3 + and CCR5 + cells were observed in these lesions. Cells positive for STAT1 and chemokine CXCL9, interferon- (IFN)-induced gene products, and pSTAT1 were also observed in the same lesions. Double immunofluorescence staining demonstrated that the cells that were positive for CD163 were also positive for STAT1. CD163 + TAMs in oral premalignant lesions coexpress CD163 and STAT1, suggesting that the TAMs in oral premalignant lesions possess an M1 phenotype in a Th1-dominated micromilieu

NICMOS POLARIMETRY OF 'POLAR-SCATTERED' SEYFERT 1 GALAXIES

International Nuclear Information System (INIS)

Batcheldor, D.; Robinson, A.; Axon, D. J.; Young, S.; Quinn, S.; Smith, J. E.; Hough, J.; Alexander, D. M.

2011-01-01

The nuclei of Seyfert 1 galaxies exhibit a range of optical polarization characteristics that can be understood in terms of two scattering regions producing orthogonal polarizations: an extended polar scattering region (PSR) and a compact equatorial scattering region (ESR), located within the circum-nuclear torus. Here we present NICMOS 2.0 μm imaging polarimetry of six 'polar-scattered' Seyfert 1 (S1) galaxies, in which the PSR dominates the optical polarization. The unresolved nucleus ( 2μm ) is consistent with the average for the optical spectrum(θ v ), implying that the nuclear polarization is dominated by polar scattering at both wavelengths. The same is probably true for NGC 3227. In both NGC 4593 and Mrk 766, there is a large difference between θ 2μm and θ v off-nucleus, where polar scattering is expected to dominate. This may be due to contamination by interstellar polarization in NGC 4593, but there is no clear explanation in the case of the strongly polarized Mrk 766. Lastly, in Mrk 1239, a large change (∼60 0 ) in θ 2 μ m between the nucleus and the annulus indicates that the unresolved nucleus and its immediate surroundings have different polarization states at 2 μm, which we attribute to the ESR and PSR, respectively. A further implication is that the source of the scattered 2 μm emission in the unresolved nucleus is the accretion disk, rather than torus hot dust emission.

Cygnus X-1: Discovery of variable circular polarization

International Nuclear Information System (INIS)

Michalsky, J.J.; Swedlund, J.B.; Stokes, R.A.

1975-01-01

HDE 226868, the optical counterpart of Cyg X-1, has been observed for circular polarization during 1974. Observations in five colors suggest that circular polarization results from an interstellar effect. Measurements of the blue polarization reveal circular polarization variations synchronous with the 5)./sub /6 orbital period. The circular polarization variation appears to be similar to the blue intensity variation

Circulating endothelial progenitor cells, Th1/Th2/Th17-related cytokines, and endothelial dysfunction in resistant hypertension.

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Magen, Eli; Feldman, Arie; Cohen, Ziona; Alon, Dora Ben; Minz, Evegeny; Chernyavsky, Alexey; Linov, Lina; Mishal, Joseph; Schlezinger, Menacham; Sthoeger, Zev

2010-02-01

A possible link between chronic vascular inflammation and arterial hypertension is now an object of intensive studies. To compare Th1/Th2/Th17 cells-related cytokines, circulating endothelial progenitor cells (EPC), and endothelial function in subjects with resistant arterial hypertension (RAH) and controlled arterial hypertension (CAH). Blood pressure was measured by electronic sphygmomanometer. EPC were identified as CD34+/CD133+/kinase insert domain receptor (KDR)+ cells by flow cytometry. Th1/Th2/Th17 cells-related cytokines were identified using the Human Th1/Th2/Th17 Cytokines MultiAnalyte ELISArray Kit. Endothelium-dependent (FMD) vasodilatation of brachial artery was measured by Doppler ultrasound scanning. RAH group (n = 20) and CAH group (n = 20) and 17 healthy individuals (control group) were recruited. In the RAH group, lower blood levels of EPC number (42.4 +/- 16.7 cells/mL) and EPC% (0.19 +/- 0.08%) were observed than in the CAH group (93.1 +/- 88.7 cells/mL; P = 0.017; 0.27 +/- 0.17; P = 0.036) and control group (68.5 +/- 63.6 cells/mL; P < 0.001; 0.28 +/- 0.17%; P = 0.003), respectively. Plasma transforming growth factor-beta1 levels were significantly higher in the RAH group (1767 +/- 364 pg/mL) than in the CAH group (1292 +/- 349; P < 0.001) and in control group (1203 +/- 419 pg/mL; P < 0.001). In the RAH group, statistically significant negative correlation was observed between systolic blood pressure and EPC% (r = -0.72, P < 0.01). FMD in the RAH group was significantly lower (5.5 +/- 0.8%) than in the CAH group (9.2 +/- 1.4; P < 0.001) and in healthy controls (10.1 +/- 1.1%; P < 0.001). RAH is characterized by reduced circulating EPC, substantial endothelial dysfunction, and increased plasma transforming growth factor-beta1 levels.

Th1, Th17, CXCL16 and homocysteine elevated after intracranial and cervical stent implantation.

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Tang, Yanyan; Wei, Yunfei; Ye, Ziming; Qin, Chao

2017-08-01

The presence of Th1 and Th17 cells has been observed as major inducers in inflammation and immune responses associated stenting. However, there is rare data on the impact of Th1, Th17, CXCL16 and homocysteine after cerebral stent implantation. Here, we performed the statistical analysis to first evaluate the variation of the Th17and Th1 cells and their related cytokines, CXCL16 and homocysteine in the peripheral blood of patients with cerebral stenting. The flow cytometry was used to detect the proportion of Th1 and Th17 cells in peripheral blood mononuclear cells (PBMCs). The enzyme-linked immunosorbent assay was used to measure the serum concentrations of IFN-γ, IL-17 and CXCL16. Plasma homocysteine was examined by immunoturbidimetry. The level of Th1, CXCL16 and homocysteine showed an increase at 3 d, followed by the continuous decrease at 7 d and 3 months. The frequency of Th17 cells increased to a peak at three days, and subsequently decreased with a higher level than baseline. Our data revealed that the variation in Th1, Th17, CXCL16 and homocysteine in peripheral blood of patients with stenting may be implicated in inflammation after intracranial and cervical stent implantation. A better understanding of these factors will provide help for further drug design and clinical therapy.

Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance

Science.gov (United States)

Martino, Matteo; Rocchi, Giulio; Escelsior, Andrea; Fornaro, Michele

2012-01-01

Neurotransmitters and hormones regulate major immune functions, including the selection of T helper (Th)1 or Th2 cytokine responses, related to cell-mediated and humoral immunity, respectively. A role of imbalance and dynamic switching of Th1/Th2 system has been proposed, with relative displacement of the immune reserve in relation to complex interaction between Th1/Th2 and neuro-hormonal balance fluctuations, in the pathogenesis of various chronic human diseases, probably also including psychiatric disorders. Components of the stress system such as norepinephrine (NE) and glucocorticoids appear to mediate a Th2 shift, while serotonin (5-HT) and melatonin might mediate a Th1 shift. Some antidepressants would occur affecting these systems, acting on neurotransmitter balance (especially the 5-HT/NE balance) and expression levels of receptor subtypes, which in turn affect cytokine production and relative Th1/Th2 balance. It could be therefore hypothesized that the antidepressant-related increase in NE tone enhances the Th2 response, while the decrease in NE tone or the increase in 5-HT tone enhances the Th1 response. However, the neurotransmitter and Th1/Th2 balance modulation could be relative, aiming to restore physiological levels a previous imbalance in receptor sensitivity and cytokine production. The considerations on neuro-immunomodulation could represent an additional aid in the study of pathophysiology of psychiatric disorders and in the choice of specific antidepressants in specific clusters of symptoms, especially in comorbidity with internal pathologies. Furthermore limited data, reviewed here, have shown the effectiveness of some antidepressants as pure immunomodulators. However, these considerations are tentative and require experimental confirmation or refutation by future studies. PMID:23204981

Nuclear Physics Department: Progress report from the 1st October 1988 to the 30th September 1990

International Nuclear Information System (INIS)

1990-01-01

The work performed at the Nuclear Physics Department, from the 1st October 1988 to the 30th September 1990, are summarized. The investigations are carried out in the fields of heavy ion physics, intermediate energy physics and accelerators using superconducting cavities. Theoretical and experimental studies accomplished in the following fields are included: hot nuclei, exotic nuclei, giant resonances, fission, inelastic scattering, electroproduction of pions, polarization of deuterons, central collisions [fr

Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, TH1, TH17 and TREG cells

Directory of Open Access Journals (Sweden)

Gjertsen Bjørn

2010-07-01

Full Text Available Abstract Background Several observations suggest that immunological events early after chemotherapy, possibly during the period of severe treatment-induced cytopenia, are important for antileukemic immune reactivity in acute myeloid leukemia (AML. We therefore investigated the frequencies of various T cell subsets (TC1, TH1, TH17 and CD25+ FoxP3+ TREG cells in AML patients with untreated disease and following intensive chemotherapy. Results Relative levels of circulating TC1 and TH1 cells were decreased in patients with severe chemotherapy-induced cytopenia, whereas TH17 levels did not differ from healthy controls. Increased levels of regulatory CD25+ FoxP3+ T cells were detected in AML patients with untreated disease, during chemotherapy-induced cytopenia and during regeneration after treatment. TH17 and TH1 levels were significantly higher in healthy males than females, but this gender difference was not detected during chemotherapy-induced cytopenia. Finally, exogenous IL17-A usually had no or only minor effects on proliferation of primary human AML cells. Conclusions We conclude that the effect of intensive AML chemotherapy differ between circulating T cell subsets, relative frequencies of TH17 cells are not affected by chemotherapy and this subset may affect AML cells indirectly through their immunoregulatory effects but probably not through direct effects of IL17-A.

The Th1:Th2 Dichotomy of Pregnancy and Preterm Labour

Directory of Open Access Journals (Sweden)

Lynne Sykes

2012-01-01

Full Text Available Pregnancy is a unique immunological state in which a balance of immune tolerance and suppression is needed to protect the fetus without compromising the mother. It has long been established that a bias from the T helper 1 cytokine profile towards the T helper 2 profile contributes towards successful pregnancy maintenance. The majority of publications that report on aberrant Th1:Th2 balance focus on early pregnancy loss and preeclampsia. Over the last few decades, there has been an increased awareness of the role of infection and inflammation in preterm labour, and the search for new biomarkers to predict preterm labour continues. In this paper, we explore the evidence for an aberrant Th1:Th2 profile associated with preterm labour. We also consider the potential for its use in screening women at high risk of preterm labour and for prophylactic therapeutic measures for the prevention of preterm labour and associated neonatal adverse outcomes.

Electron cyclotron current drive experiments in LHCD plasmas using a remote steering antenna on the TRIAM-1M tokamak

International Nuclear Information System (INIS)

Idei, H.; Hanada, K.; Zushi, H.; Ohkubo, K.; Hasegawa, M.; Kubo, S.; Nishi, S.; Fukuyama, A.; Sato, K.N.; Nakamura, K.; Sakamoto, M.; Iyomasa, A.; Kawasaki, S.; Nakashima, H.; Higashijima, A.; Notake, T.; Shimozuma, T.; Ito, S.; Hoshika, H.; Maezono, N.; Nakashima, K.; Ogawa, M.

2006-01-01

A remote steering antenna was recently developed for electron cyclotron heating and current drive (ECH/ECCD) experiments on the TRIAM-1M tokamak. This is the first application of the remote steering antenna concept for ECH/ECCD experiments, which have conditions relevant to the International Thermonuclear Experimental Reactor (ITER). Fundamental ECH and ECCD experiments were conducted in the ITER frequency from the low field using this antenna system. In addition to the angles near 0 0 , the launcher was a symmetric direction antenna with an extended steering-angle capability of ±(8 0 -19 0 ). The output beam from the antenna was a well-defined Gaussian with a proper steering angle. The Gaussian content and the steering-angle accuracy were 0.85 and -0.5 0 , respectively. The high power tests measured the antenna transmission efficiency at 0.90-0.94. The efficiencies obtained in the low and high power tests were consistent with the calculations using higher-order modes. In order to excite the pure O/X-modes in the oblique injection, two polarizers were used to control the elliptical polarization of the incident beam for the ECCD experiments. The fundamental O/X-mode ECH/ECCD was applied to lower hyrid current drive plasmas at the optimized incident polarization. In the X-mode experiment, at medium density (∼1 x 10 19 m -3 ), clear differences in the plasma current and the hard x-ray intensity were observed between the co- and counter-steering injections due to the ECCD effect on the coupling of forward fast electrons

The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells

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Amarnath, Shoba; Mangus, Courtney W.; Wang, James C.M.; Wei, Fang; He, Alice; Kapoor, Veena; Foley, Jason E.; Massey, Paul R.; Felizardo, Tania C.; Riley, James L.; Levine, Bruce L.; June, Carl H.; Medin, Jeffrey A.; Fowler, Daniel H.

2011-01-01

Immune surveillance by T helper type 1 (Th1) cells is critical for the host response to tumors and infection, but also contributes to autoimmunity and graft-versus-host disease (GvHD) after transplantation. The inhibitory molecule programmed death ligand-1 (PDL1) has been shown to anergize human Th1 cells, but other mechanisms of PDL1-mediated Th1 inhibition such as the conversion of Th1 cells to a regulatory phenotype have not been well characterized. We hypothesized that PDL1 may cause Th1 cells to manifest differentiation plasticity. Conventional T cells or irradiated K562 myeloid tumor cells overexpressing PDL1 converted TBET+ Th1 cells into FOXP3+ regulatory T cells (TREGS) in vivo, thereby preventing human-into-mouse xenogeneic GvHD (xGvHD). Either blocking PD1 expression on Th1 cells by siRNA targeting or abrogation of PD1 signaling by SHP1/2 pharmacologic inhibition stabilized Th1 cell differentiation during PDL1 challenge and restored the capacity of Th1 cells to mediate lethal xGVHD. PD1 signaling therefore induces human Th1 cells to manifest in vivo plasticity, resulting in a TREG phenotype that severely impairs cell-mediated immunity. Converting human Th1 cells to a regulatory phenotype with PD1 signaling provides a potential way to block GvHD after transplantation. Moreover, because this conversion can be prevented by blocking PD1 expression or pharmacologically inhibiting SHP1/2, this pathway provides a new therapeutic direction for enhancing T cell immunity to cancer and infection. PMID:22133721

Effectors of Th1 and Th17 cells act on astrocytes and augment their neuroinflammatory properties.

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Prajeeth, Chittappen K; Kronisch, Julius; Khorooshi, Reza; Knier, Benjamin; Toft-Hansen, Henrik; Gudi, Viktoria; Floess, Stefan; Huehn, Jochen; Owens, Trevor; Korn, Thomas; Stangel, Martin

2017-10-16

Autoreactive Th1 and Th17 cells are believed to mediate the pathology of multiple sclerosis in the central nervous system (CNS). Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of the neuroinflammation. Previously, we have shown that only Th1 but not Th17 effectors activate microglia. However, it is not clear which cells are targets of Th17 effectors in the CNS. To understand the effects driven by Th17 cells in the CNS, we induced experimental autoimmune encephalomyelitis in wild-type mice and CD4 + T cell-specific integrin α4-deficient mice where trafficking of Th1 cells into the CNS was affected. We compared microglial and astrocyte response in the brain and spinal cord of these mice. We further treated astrocytes with supernatants from highly pure Th1 and Th17 cultures and assessed the messenger RNA expression of neurotrophic factors, cytokines and chemokines, using real-time PCR. Data obtained was analyzed using the Kruskal-Wallis test. We observed in α4-deficient mice weak microglial activation but comparable astrogliosis to that of wild-type mice in the regions of the brain populated with Th17 infiltrates, suggesting that Th17 cells target astrocytes and not microglia. In vitro, in response to supernatants from Th1 and Th17 cultures, astrocytes showed altered expression of neurotrophic factors, pro-inflammatory cytokines and chemokines. Furthermore, increased expression of chemokines in Th1- and Th17-treated astrocytes enhanced recruitment of microglia and transendothelial migration of Th17 cells in vitro. Our results demonstrate the delicate interaction between T cell subsets and glial cells and how they communicate to mediate their effects. Effectors of Th1 act on both microglia and astrocytes whereas Th17 effectors preferentially target astrocytes to promote neuroinflammation.

Liposome delivery of Chlamydia muridarum major outer membrane protein primes a Th1 response that protects against genital chlamydial infection in a mouse model

DEFF Research Database (Denmark)

Hansen, Jon; Jensen, Klaus Thorleif; Follmann, Frank

2008-01-01

BACKGROUND: Immunity to chlamydia is thought to rely on interferon (IFN)-gamma-secreting T helper cells type 1 (Th1) with an additional effect of secreted antibodies. A need for Th1-polarizing adjuvants in experimental chlamydia vaccines has been demonstrated, and antigen conformation has also been......-alpha and a profoundly reduced vaginal chlamydial load, compared with control mice. The protection was CD4(+) T cell dependent and was not dependent on MOMP conformation. CONCLUSION: CAF01 adjuvant facilitates a protective anti-MOMP CD4(+) T cell response independent of MOMP conformation....

Biglycan, a novel trigger of Th1 and Th17 cell recruitment into the kidney.

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Nastase, Madalina-Viviana; Zeng-Brouwers, Jinyang; Beckmann, Janet; Tredup, Claudia; Christen, Urs; Radeke, Heinfried H; Wygrecka, Malgorzata; Schaefer, Liliana

2017-12-15

Th1 and Th17 cells, T helper (Th) subtypes, are key inducers of renal fibrosis. The molecular mechanisms of their recruitment into the kidney, however, are not well understood. Here, we show that biglycan, a proteoglycan of the extracellular matrix, acting in its soluble form as a danger signal, stimulates autonomously the production of Th1 and Th17 chemoattractants CXCL10 and CCL20 in macrophages. In the presence of IFNγ, biglycan synergistically stimulates CXCL9. In macrophages deficient for TLR2, TLR4, and their adaptor molecules MyD88 or TRIF, we identified highly selective mechanisms of biglycan-dependent Th1/17 chemoattraction. Thus, the expression of CXCL9 and CXCL10, common chemoattractants for CXCR3-positive Th1 and Th17 cells, is triggered in a biglycan-TLR4/TRIF-dependent manner. By contrast, biglycan induces CCL20 chemokine production, responsible for CCR6-positive Th17 cell recruitment, in a TLR2/4/MyD88-dependent manner. Importantly, at the onset of diabetes mellitus and lupus nephritis we provide evidence for biglycan-dependent recruitment of Th1 and Th17 cells, IFNγ and IL-17 production, and development of albuminuria in mice lacking or overexpressing soluble biglycan. Furthermore, by genetic ablation of Cxcl10 we showed in vivo involvement of this chemokine in biglycan-dependent recruitment of Th1 and Th17 cells into the kidney. Finally, a positive correlation of biglycan and CXCL10/CXCL9 levels was detected in plasma from patients with diabetic nephropathy and lupus nephritis. Taken together, we identified biglycan as a novel trigger of Th1 and Th17 cell recruitment into the kidney and we postulate that interfering with biglycan/TLR/TRIF/MyD88-signaling might provide novel therapeutic avenues for renal fibrosis. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Impediment to Spirit Drive on Sol 1806

Science.gov (United States)

2009-01-01

The hazard avoidance camera on the front of NASA's Mars Exploration Rover Spirit took this image after a drive by Spirit on the 1,806th Martian day, or sol, (January 31, 2009) of Spirit's mission on the surface of Mars. The wheel at the bottom right of the image is Spirit's right-front wheel. Because that wheel no longer turns, Spirit drives backwards dragging that wheel. The drive on Sol 1806 covered about 30 centimeters (1 foot). The rover team had planned a longer drive, but Spirit stopped short, apparently from the right front wheel encountering the partially buried rock visible next to that wheel. The hazard avoidance cameras on the front and back of the rover provide wide-angle views. The hill on the horizon in the right half of this image is Husband Hill. Spirit reached the summit of Husband Hill in 2005.

T-cell clones from Th1, Th17 or Th1/17 lineages and their signature cytokines have different capacity to activate endothelial cells or synoviocytes.

Science.gov (United States)

Lavocat, Fabien; Maggi, Laura; Annunziato, Francesco; Miossec, Pierre

2016-12-01

To compare the direct effect of cytokines on synoviocytes and endothelial cells to the effects of supernatants from Th1, Th17 and Th1/17 clones and the direct cell-cell interactions with the same clones. Th17 and Th1/17 clones were obtained from the CD161+CCR6+ fraction and Th1 clones from the CD161-CCR6- fraction of human CD4+ T-cells. Endothelial cells or synoviocytes were cultured in the presence of either isolated pro-inflammatory cytokines (IL-17 and/or TNF-α) or supernatants from the T-cell clones or co-cultured with T-cell clones themselves. IL-6 and IL-8 expression and production were analyzed. IL-17 and TNF-α induced IL-6 and IL-8 expression, although IL-17 alone had a limited effect on endothelial cells compared to synoviocytes. Supernatants from activated T-helper clones also induced IL-6 and IL-8 expression but with discrepancies between endothelial cells and synoviocytes. Endothelial cells were mostly activated by Th1 clone supernatants whereas synoviocytes were activated by all T-cell subtypes. Finally, cell-cell contact experiments showed a great heterogeneity among cell clones, even from the same lineage. IL-6 expression was mostly induced by contact with Th1 clones both in endothelial and mesenchymal cells whereas IL-8 expression was induced by all T-cell clones whatever their phenotype. We showed that endothelial cells were much more sensitive to Th1 activation whereas synoviocytes were activated by all T-helper lineages. This work highlights the heterogeneity of interactions between T-cells and stromal cells through soluble factors or direct cell contact. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nocardia rubra cell-wall skeleton promotes CD4+ T cell activation and drives Th1 immune response.

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Wang, Guangchuan; Wu, Jie; Miao, Miao; Dou, Heng; Nan, Ning; Shi, Mingsheng; Yu, Guang; Shan, Fengping

2017-08-01

Several lines of evidences have shown that Nocardia rubra cell wall skeleton (Nr-CWS) has immunoregulatory and anti-tumor activities. However, there is no information about the effect of Nr-CWS on CD4 + T cells. The aim of this study was to explore the effect of Nr-CWS on the phenotype and function of CD4 + T cells. Our results of in vitro experiments showed that Nr-CWS could significantly up-regulate the expression of CD69 and CD25 on CD4 + T cells, promote the proliferation of CD4 + T cells, increase the production of IFN-γ, TNF-α and IL-2 in the supernatants, but has no significant effect on the apoptosis and death of CD4 + T cells. Results of in vivo experiments showed that Nr-CWS could promote the proliferation of CD4 + T cells, and increase the production of IL-2, IFN-γ and TNF-α (Th1 type cytokines). These data suggest that Nr-CWS can enhance the activation of CD4 + T cells, promote the proliferation of CD4 + T cells and the differentiation of CD4 + T cells to Th1 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

PTEN drives Th17 cell differentiation by preventing IL-2 production.

Science.gov (United States)

Kim, Hyeong Su; Jang, Sung Woong; Lee, Wonyong; Kim, Kiwan; Sohn, Hyogon; Hwang, Soo Seok; Lee, Gap Ryol

2017-11-06

T helper 17 (Th17) cells are a CD4 + T cell subset that produces IL-17A to mediate inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However, the mechanism by which IL-2 is suppressed during Th17 cell differentiation remains unclear. Here, we show that phosphatase and tensin homologue (PTEN) is a key factor that regulates Th17 cell differentiation by suppressing IL-2 production. Th17-specific Pten deletion ( Pten fl/fl Il17a cre ) impairs Th17 cell differentiation in vitro and ameliorated symptoms of experimental autoimmune encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease. Mechanistically, Pten deficiency up-regulates IL-2 and phosphorylation of STAT5, but reduces STAT3 phosphorylation, thereby inhibiting Th17 cell differentiation. PTEN inhibitors block Th17 cell differentiation in vitro and in the EAE model. Thus, PTEN plays a key role in Th17 cell differentiation by blocking IL-2 expression. © 2017 Kim et al.

IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures

DEFF Research Database (Denmark)

Blom, Lars; Poulsen, Lars K.

2012-01-01

The IL-1 family members IL-1ß, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood...... donors, and reactivated in the presence of IL-1ß, IL-18, or IL-33. Interestingly, we observe modifying responses in Th1 and Th2 cultures induced by IL-18 or IL-33 but not by IL-1ß, both contributing to amplify production of IL-5, IL-13, and IFN-¿. IL-18 or IL-33 stimulation of Th1 cultures resulted...... in increased IFN-¿ and IL-13 production concurrent with reduced IL-10 gene transcription and secretion even though Th1 cultures, in contrast to IL-18Ra, had low ST2L expression. Furthermore, adding IL-18 to Th1 cultures promoted Tbet mRNA expression and production. Th2 cultures stimulated with IL-18 or IL-33...

Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration.

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Chen, Jiajia; Wang, Wenzhan; Li, Qiuming

2017-01-01

Age-related macular degeneration (AMD) is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. We examined the CD4+ T cell compartments and their functions in AMD patients. AMD patients presented significantly higher frequencies of interferon (IFN)-γ-expressing and interleukin (IL)-17-expressing CD4+ T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4+ T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3+ and CCR4+CCR6+ expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE)-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ- and IL-17-dependent fashion, and could potentially serve as therapeutic targets. © 2017 The Author(s). Published by S. Karger AG, Basel.

Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia.

Science.gov (United States)

Janikashvili, Nona; LaCasse, Collin J; Larmonier, Claire; Trad, Malika; Herrell, Amanda; Bustamante, Sara; Bonnotte, Bernard; Har-Noy, Michael; Larmonier, Nicolas; Katsanis, Emmanuel

2011-02-03

Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4(+) T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4(+)CD25(+)FoxP3(+) regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3(+) Tregs from naive CD4(+)CD25(-)FoxP3(-) T cells by an interferon-γ-dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with a chaperone-rich cell lysate (CRCL) vaccine, leading to improved survival and long-lasting protection against leukemia. The combination of CRCL as a source of tumor-specific antigens and Th-1 lymphocytes as an adjuvant has the potential to stimulate efficient specific antitumor immunity while restraining Treg-induced suppression.

The Combination of Early and Rapid Type I IFN, IL-1α, and IL-1β Production Are Essential Mediators of RNA-Like Adjuvant Driven CD4+ Th1 Responses

Science.gov (United States)

Madera, Rachel F.; Wang, Jennifer P.; Libraty, Daniel H.

2011-01-01

There is a growing need for novel vaccine adjuvants that can provide safe and potent T-helper type 1 (Th1) activity. RNA-like immune response modifiers (IRMs) are candidate T-cell adjuvants that skew acquired immune responses towards a Th1 phenotype. We set out to delineate the essential signaling pathways by which the RNA-like IRMs, resiquimod (R-848) and polyinosinic:polycytidylic acid (poly I:C), augment CD4+ T-helper 1 (Th1) responses. Highly purified murine conventional dendritic cells (cDCs) and conventional CD4+ T-cells were co-cultured in allogeneic and MHC congenic mixed leukocyte reactions. The activation of CD4+ Th1 cells was examined utilizing cells from mice deficient in specific RNA-sensing pattern recognition receptors and signaling mediators. R-848 and poly I:C stimulation of Type I interferon production and signaling in cDCs was essential but not sufficient for driving CD4+ Th1 responses. The early and rapid production of IL-1α and IL-1β was equally critical for the optimal activation of Th1 CD4+ T-cells. R-848 activation of Toll-like receptor 7/MyD88-dependent signaling in cDCs led to a rapid upregulation of pro-IL-1α and pro-IL-1β production compared to poly I:C activation of MyD88-independent signaling pathways. The in vitro data show that CD4+ T-cell adjuvant activity of RNA-like IRMs is mediated by a critical combination of early and rapid Type I interferon, IL-1α and IL-1β production. These results provide important insights into the key signaling pathways responsible for RNA-like IRM CD4+ Th1 activation. A better understanding of the critical signaling pathways by which RNA-like IRMs stimulate CD4+ Th1 responses is relevant to the rational design of improved vaccine adjuvants. PMID:22206014

The combination of early and rapid type I IFN, IL-1α, and IL-1β production are essential mediators of RNA-like adjuvant driven CD4+ Th1 responses.

Directory of Open Access Journals (Sweden)

Rachel F Madera

Full Text Available There is a growing need for novel vaccine adjuvants that can provide safe and potent T-helper type 1 (Th1 activity. RNA-like immune response modifiers (IRMs are candidate T-cell adjuvants that skew acquired immune responses towards a Th1 phenotype. We set out to delineate the essential signaling pathways by which the RNA-like IRMs, resiquimod (R-848 and polyinosinic:polycytidylic acid (poly I:C, augment CD4+ T-helper 1 (Th1 responses. Highly purified murine conventional dendritic cells (cDCs and conventional CD4+ T-cells were co-cultured in allogeneic and MHC congenic mixed leukocyte reactions. The activation of CD4+ Th1 cells was examined utilizing cells from mice deficient in specific RNA-sensing pattern recognition receptors and signaling mediators. R-848 and poly I:C stimulation of Type I interferon production and signaling in cDCs was essential but not sufficient for driving CD4+ Th1 responses. The early and rapid production of IL-1α and IL-1β was equally critical for the optimal activation of Th1 CD4+ T-cells. R-848 activation of Toll-like receptor 7/MyD88-dependent signaling in cDCs led to a rapid upregulation of pro-IL-1α and pro-IL-1β production compared to poly I:C activation of MyD88-independent signaling pathways. The in vitro data show that CD4+ T-cell adjuvant activity of RNA-like IRMs is mediated by a critical combination of early and rapid Type I interferon, IL-1α and IL-1β production. These results provide important insights into the key signaling pathways responsible for RNA-like IRM CD4+ Th1 activation. A better understanding of the critical signaling pathways by which RNA-like IRMs stimulate CD4+ Th1 responses is relevant to the rational design of improved vaccine adjuvants.

Association between Th1/Th2 immune imbalance and obesity in women with or without polycystic ovary syndrome.

Science.gov (United States)

Gong, Ping; Shi, Bingwei; Wang, Juan; Cao, Peixia; Diao, Zhenyu; Wang, Yuji; Hu, Yali; Li, Shuping

2018-02-15

This study aimed to investigate the Th1/Th2 cells in peripheral blood of PCOS patients, and assess the potential correlation between Th1/Th2 imbalance and obesity. Thirty-nine PCOS patients and 23 age-matched controls were enrolled. The PBMCs were obtained before pharmacological intervention in women with or without PCOS. The profiles of Th1 (IFN-γ) and Th2 (IL-4) cytokines of CD3 + CD - T lymphocyte subsets were analyzed by flow cytometry. Plasma sex hormones including E 2 , T, FSH, LH, and FINS, FPG were measured, together with BMI, WC, LH/FSH, E 2 /T and HOMA-IR index being calculated. Association between Th1/Th2 imbalance and BMI, WC were evaluated. The proportion of Th1 cells and Th1/Th2 ratio were significantly higher in PCOS patients than those in controls, accompanied by elevated T, LH, LH/FSH, FINS, HOMA-IR index and reduced E 2 /T. The Th1/Th2 ratio was increased when BMI and WC were enhanced in PCOS. Moreover, the significant difference of Th1/Th2 ratio was observed between WC subgroups of PCOS. It is concluded that Th1 type immunity is predominant in systemic immunization of PCOS patients. Th1/Th2 immune imbalance is connected with obesity, especially abdominal obesity, and may be one of the underlying mechanism for the pathogenesis of PCOS.

TNF-α inhibitors reduce the pathological Th1 -Th17 /Th2 imbalance in cutaneous mesenchymal stem cells of psoriasis patients.

Science.gov (United States)

Campanati, Anna; Orciani, Monia; Lazzarini, Raffaella; Ganzetti, Giulia; Consales, Veronica; Sorgentoni, Giulia; Di Primio, Roberto; Offidani, Annamaria

2017-04-01

Psoriasis is a disease characterized by an imbalance between Th 1 and Th 17 and Th 2 inflammatory axes, in which cutaneous mesenchymal stem cells (MSCs) are early involved, as they show a greater relative expression of several genes encoding for Th 1 and Th 17 cytokines. Therapeutic implications of TNF-α inhibitors on differentiated skin cells have been largely described in psoriasis; however, their effects on MSCs derived from patients with psoriasis have been only partially described. The aim of this work was to evaluate the effect of TNF-α inhibitors on cytokine milieu expressed by MSCs isolated from the skin of patients with psoriasis. Resident MSCs from skin of patients with psoriasis and healthy subjects have been isolated, characterized and profiled by PCR and ELISA for the expression of 22 cytokines involved in Th 1 , Th 2 and Th 17 pathways, both before and after 12 weeks therapy with TNF-α inhibitors. The administration of TNF-α inhibitors for 12-weeks acts on MSCs as follows: it reduces the expression of several Th 1 -Th 17 cytokines whose levels are elevated at baseline (IL-6, IL-8, IL-12, IL-23A, IFN-γ, TNF-α, CCL2, CCL20, CXCL2, CXCL5, IL-17A, IL-17C, IL-17F, IL-21, G-CSF). Similarly, it enhances the expression of several Th 2 cytokines which are underexpressed at baseline (IL-2, IL-4, IL-5), reducing the expression of those overexpressed at baseline (TGF-β and IL-13). TNF-α inhibitors could contribute to reduce the pathological imbalance between the Th 1 -Th 17 vs Th 2 axis in MSCs of patients with psoriasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes

Science.gov (United States)

Dubovsky, Jason A.; Beckwith, Kyle A.; Natarajan, Gayathri; Woyach, Jennifer A.; Jaglowski, Samantha; Zhong, Yiming; Hessler, Joshua D.; Liu, Ta-Ming; Chang, Betty Y.; Larkin, Karilyn M.; Stefanovski, Matthew R.; Chappell, Danielle L.; Frissora, Frank W.; Smith, Lisa L.; Smucker, Kelly A.; Flynn, Joseph M.; Jones, Jeffrey A.; Andritsos, Leslie A.; Maddocks, Kami; Lehman, Amy M.; Furman, Richard; Sharman, Jeff; Mishra, Anjali; Caligiuri, Michael A.; Satoskar, Abhay R.; Buggy, Joseph J.; Muthusamy, Natarajan; Johnson, Amy J.

2013-01-01

Given its critical role in T-cell signaling, interleukin-2–inducible kinase (ITK) is an appealing therapeutic target that can contribute to the pathogenesis of certain infectious, autoimmune, and neoplastic diseases. Ablation of ITK subverts Th2 immunity, thereby potentiating Th1-based immune responses. While small-molecule ITK inhibitors have been identified, none have demonstrated clinical utility. Ibrutinib is a confirmed irreversible inhibitor of Bruton tyrosine kinase (BTK) with outstanding clinical activity and tolerability in B-cell malignancies. Significant homology between BTK and ITK alongside in silico docking studies support ibrutinib as an immunomodulatory inhibitor of both ITK and BTK. Our comprehensive molecular and phenotypic analysis confirms ITK as an irreversible T-cell target of ibrutinib. Using ibrutinib clinical trial samples along with well-characterized neoplastic (chronic lymphocytic leukemia), parasitic infection (Leishmania major), and infectious disease (Listeria monocytogenes) models, we establish ibrutinib as a clinically relevant and physiologically potent ITK inhibitor with broad therapeutic utility. This trial was registered at www.clinicaltrials.gov as #NCT01105247 and #NCT01217749. PMID:23886836

Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes.

Science.gov (United States)

Dubovsky, Jason A; Beckwith, Kyle A; Natarajan, Gayathri; Woyach, Jennifer A; Jaglowski, Samantha; Zhong, Yiming; Hessler, Joshua D; Liu, Ta-Ming; Chang, Betty Y; Larkin, Karilyn M; Stefanovski, Matthew R; Chappell, Danielle L; Frissora, Frank W; Smith, Lisa L; Smucker, Kelly A; Flynn, Joseph M; Jones, Jeffrey A; Andritsos, Leslie A; Maddocks, Kami; Lehman, Amy M; Furman, Richard; Sharman, Jeff; Mishra, Anjali; Caligiuri, Michael A; Satoskar, Abhay R; Buggy, Joseph J; Muthusamy, Natarajan; Johnson, Amy J; Byrd, John C

2013-10-10

Given its critical role in T-cell signaling, interleukin-2-inducible kinase (ITK) is an appealing therapeutic target that can contribute to the pathogenesis of certain infectious, autoimmune, and neoplastic diseases. Ablation of ITK subverts Th2 immunity, thereby potentiating Th1-based immune responses. While small-molecule ITK inhibitors have been identified, none have demonstrated clinical utility. Ibrutinib is a confirmed irreversible inhibitor of Bruton tyrosine kinase (BTK) with outstanding clinical activity and tolerability in B-cell malignancies. Significant homology between BTK and ITK alongside in silico docking studies support ibrutinib as an immunomodulatory inhibitor of both ITK and BTK. Our comprehensive molecular and phenotypic analysis confirms ITK as an irreversible T-cell target of ibrutinib. Using ibrutinib clinical trial samples along with well-characterized neoplastic (chronic lymphocytic leukemia), parasitic infection (Leishmania major), and infectious disease (Listeria monocytogenes) models, we establish ibrutinib as a clinically relevant and physiologically potent ITK inhibitor with broad therapeutic utility. This trial was registered at www.clinicaltrials.gov as #NCT01105247 and #NCT01217749.

Differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses to single epicutaneous immunization.

Science.gov (United States)

Lee, Chih-Hung; Chen, Jau-Shiuh; Chiu, Hsien-Ching; Hong, Chien-Hui; Liu, Ching-Yi; Ta, Yng-Cun; Wang, Li-Fang

2016-12-01

Epicutaneous immunization with allergens is an important sensitization route for atopic dermatitis. We recently showed in addition to the Th2 response following single epicutaneous immunization, a remarkable Th1 response is induced in B6 mice, but not in BALB/c mice, mimicking the immune response to allergens in human non-atopics and atopics. We investigated the underlying mechanisms driving this differential Th1 response between BALB/c and B6 mice. We characterized dermal dendritic cells by flow cytometric analysis. We measured the induced Th1/Th2 responses by measuring the IFN-γ/IL-13 contents of supernatants of antigen reactivation cultures of lymph node cells. We demonstrate that more dermal dendritic cells with higher activation status migrate into draining lymph nodes of B6 mice compared to BALB/c mice. Dermal dendritic cells of B6 mice have a greater ability to capture protein antigen than those of BALB/c mice. Moreover, increasing the activation status or amount of captured antigen in dermal dendritic cells induced a Th1 response in BALB/c mice. Further, differential activation behavior, but not antigen-capturing ability of dermal dendritic cells between BALB/c and B6 mice is dendritic cell-intrinsic. These results show that the differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses following single epicutaneous immunization. Furthermore, our findings highlight the potential differences between human atopics and non-atopics and provide useful information for the prediction and prevention of atopic diseases. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Recent results from the first polar direct drive plastic capsule implosions on NIF

Science.gov (United States)

Schmitt, Mark J.

2012-10-01

Polar direct drive (PDD) offers a simplified platform for conducting strongly driven implosions on NIF to investigate mix, hydro-burn and ignition-relevant physics. Its successful use necessitates a firm understanding and predictive capability of its implosion characteristics including hydro performance, symmetry and yield. To assess this capability, the first two PDD implosions of deuterium filled CH capsules were recently conducted at NIF. The P2 Legendre mode symmetry seen in these implosions agreed with pre-shot predictions even though the 700kJ drive energy produced intensities that far exceeded thresholds for both Raman and Brillouin stimulated scattering. These shots were also the first to employ image backlighting driven by two laser quads. Preliminary results indicate that the yield from the uncoated 2.25 mm diameter, 42 μm thick, CH shells was reduced by about a factor of two owing to as-shot laser drive asymmetries. Similarly, a small (sim50 μm) centroid offset between the upper and lower shell hemispheres seen in the first shot appears to be indicative of the laser quad energies. Overall, the implosion trajectories agreed with pre-shot predictions of bangtime. The second shot incorporated an 80 ?m wide,10 ?m deep depression encircling the equator of the capsule. This engineered feature was imposed to test our capability to predict the effect of high-mode features on yield and mix. A predicted yield reduction factor of 3 was not observed.[4pt] In collaboration with P. A. Bradley, J. A. Cobble, P. Hakel, S. C. Hsu, N. S. Krasheninnikova, G. A. Kyrala, G. R. Magelssen, T. J. Murphy, K. A. Obrey, R. C. Shah, I. L. Tregillis and F. J. Wysocki of Los Alamos National Laboratory; M. Marinak, R. Wallace, T. Parham, M. Cowan, S. Glenn, R. Benedetti and the NIF Operations Team of Lawrence Livermore National Laboratory; R. S. Craxton and P. W. McKenty of the Univ. Rochester; P. Fitzsimmons and A. Nikroo of General Atomics; H. Rinderknecht, M. Rosenberg, and M. G

Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their Derivatives: A Systematic Review.

Science.gov (United States)

Asadi-Samani, Majid; Bagheri, Nader; Rafieian-Kopaei, Mahmoud; Shirzad, Hedayatollah

2017-08-01

Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant-based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Effectors of Th1 and Th17 cells act on astrocytes and augment their neuroinflammatory properties

DEFF Research Database (Denmark)

Prajeeth, Chittappen K; Kronisch, Julius; Khorooshi, Reza M. H.

2017-01-01

Background: Autoreactive Th1 and Th17 cells are believed to mediate the pathology of multiple sclerosis in the central nervous system (CNS). Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of the neuroinflammation. Previously we have shown that only Th1...... mice where trafficking of Th1 cells into the CNS was affected. We compared microglia and astrocyte response in the brain and spinal cord of these mice. We further treated astrocytes with supernatants from highly pure Th1 and Th17 cultures and assessed the mRNA expression of neurotrophic factors......, cytokines and chemokines using real-time PCR. Data obtained was analysed using Kruskal- Wallis test. Results: We observed in α4-deficient mice weak microglial activation but comparable astrogliosis to that of wild-type mice in the regions of the brain populated with Th17 infiltrates suggesting that Th17...

Natural killer cells regulate Th1/Treg and Th17/Treg balance in chlamydial lung infection.

Science.gov (United States)

Li, Jing; Dong, Xiaojing; Zhao, Lei; Wang, Xiao; Wang, Yan; Yang, Xi; Wang, Hong; Zhao, Weiming

2016-07-01

Natural killer (NK) cell is an important component in innate immunity, playing a critical role in bridging innate and adaptive immunity by modulating the function of other immune cells including T cells. In this study, we focused on the role of NK cells in regulating Th1/Treg and Th17/Treg balance during chlamydial lung infection. We found that NK cell-depleted mice showed decreased Th1 and Th17 cells, which was correlated with reduced interferon-γ, interleukin (IL)-12, IL-17 and IL-22 production as well as T-bet and receptor-related orphan receptor gamma t expression compared with mice treated with the isotype control antibody. In contrast, NK cell depletion significantly increased Treg in cell number and related transcription factor (Foxp3) expression. The opposite trends of changes of Th1/Th17 and Treg led to significant reduction in the Th1/Treg and Th17/Treg ratios. The data implicate that NK cells play an important role in host defence against chlamydial lung infection, mainly through maintaining Th1/Treg and Th17/Treg balance. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Direct calculation of current drive efficiency in FISIC code

International Nuclear Information System (INIS)

Wright, J.C.; Phillips, C.K.; Bonoli, P.T.

1996-01-01

Two-dimensional RF modeling codes use a parameterization (1) of current drive efficiencies to calculate fast wave driven currents. This parameterization assumes a uniform quasi-linear diffusion coefficient and requires a priori knowledge of the wave polarizations. These difficulties may be avoided by a direct calculation of the quasilinear diffusion coefficient from the Kennel-Englemann form with the field polarizations calculated by the full wave code, FISIC (2). Current profiles are calculated using the adjoint formulation (3). Comparisons between the two formulations are presented. copyright 1996 American Institute of Physics

The Balance of Th1/Th2 and LAP+Tregs/Th17 Cells Is Crucial for Graft Survival in Allogeneic Corneal Transplantation

Directory of Open Access Journals (Sweden)

Shang Li

2018-01-01

Full Text Available Purpose. CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs. The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. Methods. A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry. The related cytokines in aqueous humor were also analyzed. Results. The frequencies of Foxp3+Tregs, GARP+Tregs, and LAP+Tregs in the survival group were significantly higher than those in the rejection group. And the expression trend of CD4+LAP+ T cells and CD4+GARP+ T cells was consistent. The level of IFN-γ, TNF, IL-6, and IL-17A markedly increased in aqueous humor during corneal allograft rejection. The ratio of Th1/Th2 and Th17/LAP+Tregs significantly increased in the rejection group at the 3rd week after corneal transplantation. Conclusion. LAP+Tregs might be regarded as substitute for Foxp3+Tregs. The balance of Th1/Th2 and LAP+Tregs/Th17 is crucial for corneal allograft survival.

Lucan Lodge Nursing Home, Ardeevin Drive, Lucan, Co. Dublin.

LENUS (Irish Health Repository)

Brown, Aisling F

2015-01-01

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization.

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Dubrac, Alexandre; Genet, Gael; Ola, Roxana; Zhang, Feng; Pibouin-Fragner, Laurence; Han, Jinah; Zhang, Jiasheng; Thomas, Jean-Léon; Chedotal, Alain; Schwartz, Martin A; Eichmann, Anne

2016-01-26

Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here, we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for both Slit2- and VEGF-induced front-rear polarity. Selective inhibition of polarized endothelial cell migration by targeting Nck1/2 prevents hypersprouting induced by Notch or Bmp signaling inhibition, and pathological ocular neovascularization and wound healing, as well. These data reveal a novel signal integration mechanism involving NCK1/2, ROBO1/2, and VEGFR2 that controls endothelial cell front-rear polarity during sprouting angiogenesis. © 2015 American Heart Association, Inc.

Electron-Spin Filters Would Offer Spin Polarization Greater than 1

Science.gov (United States)

Ting, David Z.

2009-01-01

A proposal has been made to develop devices that would generate spin-polarized electron currents characterized by polarization ratios having magnitudes in excess of 1. Heretofore, such devices (denoted, variously, as spin injectors, spin polarizers, and spin filters) have typically offered polarization ratios having magnitudes in the approximate range of 0.01 to 0.1. The proposed devices could be useful as efficient sources of spin-polarized electron currents for research on spintronics and development of practical spintronic devices.

Lewis Lung Cancer Cells Promote SIGNR1(CD209b)-Mediated Macrophages Polarization Induced by IL-4 to Facilitate Immune Evasion.

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Yan, Xiaolong; Li, Wenhai; Pan, Lei; Fu, Enqing; Xie, Yonghong; Chen, Min; Mu, Deguang

2016-05-01

Tumor-associated macrophages are a prominent component of lung cancer and contribute to tumor progression by facilitating the immune evasion of cancer cells. DC-SIGN (CD209) assists in the immune evasion of a broad spectrum of pathogens and neoplasms by inhibiting the maturation of DCs and subsequent cytokines production. However, the expression of DC-SIGN in macrophages and its role in mediating immune evasion in lung cancer and the underlying mechanism remain unclear. Our study aimed to identify the immunosuppressive role of SIGNR1 in murine macrophage differentiation and lung cancer progression. We found that SIGNR1-positive RAW264.7 macrophages were enriched in mixed cultures with Lewis lung cancer cells (LLC) (ratio of RAW 264.7 to LLC being 1:1) after stimulation with IL-4. Moreover, LLC-educated macrophages exhibited significantly higher levels of IL-10 but lower IL-12 in response to IL-4 treatment as determined by RT-PCR and ELISA. However, inhibition of SIGNR1 markedly hampered the production of IL-10, indicating that SIGNR1 was indispensable for IL-4+LLC induced macrophage polarization towards the M2 subtype. Furthermore, polarized M2 cells immersed in a tumor microenvironment promoted the migration of LLCs, as measured by transwell assays, but migration was suppressed after blockade of SIGNR1 using CD209b antibody. In addition, IL-4+LLC-educated macrophages reduced the proliferation of the activated T cells and reduced IFN-γ-mediated Th1 response in T cells, while SIGNR1 inhibition rescued Th1 cell functions. In conclusion, murine SIGNR1 expressed in LLC-educated macrophages appears to mediate IL-4-induced RAW264.7 macrophage polarization and thus facilitate lung cancer evasion. © 2015 Wiley Periodicals, Inc.

Isthmin 1 is a secreted protein expressed in skin, mucosal tissues, and NK, NKT, and th17 cells.

Science.gov (United States)

Valle-Rios, Ricardo; Maravillas-Montero, José L; Burkhardt, Amanda M; Martinez, Cynthia; Buhren, Bettina Alexandra; Homey, Bernhard; Gerber, Peter Arne; Robinson, Octavio; Hevezi, Peter; Zlotnik, Albert

2014-10-01

Using a comprehensive microarray database of human gene expression, we identified that in mammals, a secreted protein known as isthmin 1 (ISM1) is expressed in skin, mucosal tissues, and selected lymphocyte populations. ISM1 was originally identified in Xenopus brain during development, and it encodes a predicted ∼50-kDa protein containing a signal peptide, a thrombospondin domain, and an adhesion-associated domain. We confirmed the pattern of expression of ISM1 in both human and mouse tissues. ISM1 is expressed by DX5(+) lung lymphocytes that include NK and NKT-like cells, and is also expressed by some CD4(+) T cells upon activation but its expression increases significantly when CD4(+) T cells were polarized to the Th17 lineage in vitro. The presence of IFN-γ during CD4(+) T cell polarization inhibits ISM1 expression. Given that ISM1 has been reported to have anti-angiogenic properties, these observations suggest that ISM1 is a mediator of lymphocyte effector functions and may participate in both innate and acquired immune responses.

Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway.

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Wu, Xin; Dou, Yannong; Yang, Yan; Bian, Difei; Luo, Jinque; Tong, Bei; Xia, Yufeng; Dai, Yue

2015-08-15

Arctigenin, the main effective constituent of Arctium lappa L. fruit, has previously been proven to dramatically attenuate dextran sulfate sodium (DSS)-induced colitis in mice, a frequently used animal model of inflammatory bowel disease (IBD). As Th1 and Th17 cells play a crucial role in the pathogenesis of IBD, the present study addressed whether and how arctigenin exerted anti-colitis efficacy by interfering with the differentiation and activation of Th1/Th17 cells. In vitro, arctigenin was shown to markedly inhibit the differentiation of Th17 cells from naïve T cells, and moderately inhibit the differentiation of Th1 cells, which was accompanied by lowered phosphorylation of STAT3 and STAT4, respectively. In contrast, arctigenin was lack of marked effect on the differentiation of either Th2 or regulatory T cells. Furthermore, arctigenin was shown to suppress the mammalian target of rapamycin complex 1 (mTORC1) pathway in T cells as demonstrated by down-regulated phosphorylation of the downstream target genes p70S6K and RPS6, and it functioned independent of two well-known upstream kinases PI3K/AKT and ERK. Arctigenin was also able to inhibit the activity of mTORC1 by dissociating raptor from mTOR. Interestingly, the inhibitory effect of arctigenin on T cell differentiation disappeared under a status of mTORC1 overactivation via knockdown of tuberous sclerosis complex 2 (TSC2, a negative regulator of mTORC1) or pretreatment of leucine (an agonist of mTOR). In DSS-induced mice, the inhibition of Th1/Th17 responses and anti-colitis effect of arctigenin were abrogated by leucine treatment. In conclusion, arctigenin ameliorates colitis through down-regulating the differentiation of Th1 and Th17 cells via mTORC1 pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Arctigenin functions as a selective agonist of estrogen receptor β to restrict mTORC1 activation and consequent Th17 differentiation.

Science.gov (United States)

Wu, Xin; Tong, Bei; Yang, Yan; Luo, Jinque; Yuan, Xusheng; Wei, Zhifeng; Yue, Mengfan; Xia, Yufeng; Dai, Yue

2016-12-20

Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ERβ largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condition, suggesting that arctigenin functioned in an ERβ-dependent manner. Moreover, arctigenin was recognized to be an agonist of ERβ, which could bind to ERβ with a moderate affinity, promote dissociation of ERβ/HSP90 complex and nuclear translocation and phosphorylation of ERβ, and increase the transcription activity. Following activation of ERβ, arctigenin inhibited the activity of mTORC1 by disruption of ERβ-raptor-mTOR complex assembly. Deficiency of ERβ markedly abolished arctigenin-mediated inhibition of Th17 cell differentiation. In colitis mice, the activation of ERβ, inhibition of mTORC1 activation and Th17 response by arctigenin were abolished by PHTPP treatment. In conclusion, ERβ might be the target protein of arctigenin responsible for inhibition of mTORC1 activation and resultant prevention of Th17 cell differentiation and colitis development.

Stability, energetic particles, waves, and current drive summary

International Nuclear Information System (INIS)

Stambaugh, R.D.

2005-01-01

This is the summary paper for the subjects of plasma stability, energetic particles, waves, and current drive for the 20th IAEA Fusion Energy Conference, 1-6 November 2004, Vilamoura, Portugal. Material summarized herein was drawn from 65 contributed papers and 21 overview papers. The distribution of contributed papers by subjects is shown. Significant advances were reported on the principal instabilities in magnetically confined plasmas, even looking forward to the burning plasma state. Wave-plasma physics is maturing and novel methods of current drive and noninductive current generation are being developed. (author)

Reverse plasticity: TGF-β and IL-6 induce Th1-to-Th17-cell transdifferentiation in the gut.

Science.gov (United States)

Geginat, Jens; Paroni, Moira; Kastirr, Ilko; Larghi, Paola; Pagani, Massimiliano; Abrignani, Sergio

2016-10-01

Th17 cells are a heterogeneous population of pro-inflammatory T cells that have been shown to mediate immune responses against intestinal bacteria. Th17 cells are highly plastic and can transdifferentiate to Th1/17 cells or unconventional Th1 cells, which are highly pathogenic in animal models of immune-mediated diseases such as inflammatory bowel diseases. A recent European Journal of Immunology article by Liu et al. (Eur. J. Immunol. 2015. 45:1010-1018) showed, surprisingly, that Th1 cells have a similar plasticity, and could transdifferentiate to Th17 cells. Thus, IFN-γ-producing Th1 effector cells specific for an intestinal microbial antigen were shown to acquire IL-17-producing capacities in the gut in a mouse model of colitis, and in response to TGF-β and IL-6 in vitro. TGF-β induced Runx1, and together with IL-6 was shown to render the ROR-γt and IL-17 promoters in Th1 cells accessible for Runx1 binding. In this commentary, we discuss how this unexpected plasticity of Th1 cells challenges our view on the generation of Th1/17 cells with the capacity to co-produce IL-17 and IFN-γ, and consider possible implications of this Th1-to-Th17-cell conversion for therapies of inflammatory bowel diseases and protective immune responses against intracellular pathogens. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polarization due to dust scattering in the planetary nebula Cn1-1

International Nuclear Information System (INIS)

Bhatt, H.C.

1989-01-01

The peculiar emission-line object Cn1-1 (=HDE330036=PK330+4 degrees 1), classified both as a symbiotic star and as a planetary nebula, was detected by the Infrared Astronomical Satellite (IRAS) as a strong source of far-infrared dust in the system. Bhatt and Mallik (1986) discussed the nature of the dust in Cn1-1 and argued that the object is a Type I protoplanetary nebula in a binary system. The argument presented here is that the polarization is intrinsic to Cn1-1 and is due to scattering by large (compared to interstellar) dust grains in the protoplanetary nebula that are asymmetrically distributed around the central star. The large degree of polarization (approximately 3 percent for the Cn1-1 distance of approximately 450 pc) with a large lambda(sub max) is naturally explained if it is caused by scattering by large dust grains in the Cn1-1 nebula. Since the H(sub alpha) line is also polarized at the same level and position angle as the continuum, the dust must be asymmetrically distributed around the central star. The morphology of the protoplanetary nebula in Cn1-1 may be bipolar. Thus, the polarization observations support the suggestion that Cn1-1 is a bipolar Type I planetary nebula

Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice.

Science.gov (United States)

Zhang, Qian; Luan, Hong; Wang, Le; He, Fan; Zhou, Huan; Xu, Xiaoli; Li, Xingai; Xu, Qing; Niki, Toshiro; Hirashima, Mitsuomi; Xu, Gang; Lv, Yongman; Yuan, Jin

2014-04-15

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

Optimized design of polarizers with low ohmic loss and any polarization state for the 28 GHz QUEST ECH/ECCD system

Energy Technology Data Exchange (ETDEWEB)

Tsujimura, Toru Ii, E-mail: tsujimura.tohru@nifs.ac.jp [National Institute for Fusion Science, National Institutes of Natural Sciences, Toki 509-5292 (Japan); Idei, Hiroshi [Research Institute for Applied Mechanics, Kyushu University, Kasuga 816-8580 (Japan); Kubo, Shin; Kobayashi, Sakuji [National Institute for Fusion Science, National Institutes of Natural Sciences, Toki 509-5292 (Japan)

2017-01-15

Highlights: • Ohmic loss was calculated on the grooved mirror surface in simulated polarizers. • Polarizers with a low ohmic loss feature were optimally designed for 28 GHz. • Smooth rounded-rectangular grooves were made by mechanical machining. • The designed polarizers can realize all polarization states. - Abstract: In a high-power long-pulse millimeter-wave transmission line for electron cyclotron heating and current drive (ECH/ECCD), the ohmic loss on the grooved mirror surface of polarizers is one of the important issues for reducing the transmission loss. In this paper, the ohmic loss on the mirror surface is evaluated in simulated real-scale polarizer miter bends for different groove parameters under a linearly-polarized incident wave excitation. The polarizers with low ohmic loss are optimally designed for a new 28 GHz transmission line on the QUEST spherical tokamak. The calculated optimum ohmic loss is restricted to only less than 1.5 times as large as the theoretical loss for a copper flat mirror at room temperature. The copper rounded-rectangular grooves of the polarizers were relatively easy to make smooth in mechanical machining and the resultant surface roughness was not more than 0.15 μm, which is only 0.38 times as large as the skin depth. The combination of the designed elliptical polarizer and the polarization rotator can also realize any polarization state of the reflected wave.

The Role of Neutrophils in the Induction of Specific Th1 and Th17 during Vaccination against Tuberculosis.

Science.gov (United States)

Trentini, Monalisa M; de Oliveira, Fábio M; Kipnis, André; Junqueira-Kipnis, Ana P

2016-01-01

Mycobacterium tuberculosis causes tuberculosis (TB), a disease that killed more than 1.5 million people worldwide in 2014, and the Bacillus Calmette Guérin (BCG) vaccine is the only currently available vaccine against TB. However, it does not protect adults. Th1 and Th17 cells are crucial for TB control, as well as the neutrophils that are directly involved in DC trafficking to the draining lymph nodes and the activation of T lymphocytes during infection. Although several studies have shown the importance of neutrophils during M. tuberculosis infection, none have shown its role in the development of a specific response to a vaccine. The vaccine mc(2)-CMX was shown to protect mice against M. tuberculosis challenge, mainly due to specific Th1 and Th17 cells. This study evaluated the importance of neutrophils in the generation of the Th1- and Th17-specific responses elicited by this vaccine. The vaccine injection induced a neutrophil rich lesion with a necrotic central area. The IL-17 KO mice did not generate vaccine-specific Th1 cells. The vaccinated IL-22 KO mice exhibited Th1- and Th17-specific responses. Neutrophil depletion during vaccination abrogated the induction of Th1-specific responses and prohibited the bacterial load reduction observed in the vaccinated animals. The results show, for the first time, the role of neutrophils in the generation of specific Th1 and Th17 cells in response to a tuberculosis vaccine.

The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling.

Directory of Open Access Journals (Sweden)

Christiane Desel

Full Text Available Successful vaccination against intracellular pathogens requires the generation of cellular immune responses. Trehalose-6,6-dibehenate (TDB, the synthetic analog of the mycobacterial cord factor trehalose-6,6-dimycolate (TDM, is a potent adjuvant inducing strong Th1 and Th17 immune responses. We previously identified the C-type lectin Mincle as receptor for these glycolipids that triggers the FcRγ-Syk-Card9 pathway for APC activation and adjuvanticity. Interestingly, in vivo data revealed that the adjuvant effect was not solely Mincle-dependent but also required MyD88. Therefore, we dissected which MyD88-dependent pathways are essential for successful immunization with a tuberculosis subunit vaccine. We show here that antigen-specific Th1/Th17 immune responses required IL-1 receptor-mediated signals independent of IL-18 and IL-33-signaling. ASC-deficient mice had impaired IL-17 but intact IFNγ responses, indicating partial independence of TDB adjuvanticity from inflammasome activation. Our data suggest that the glycolipid adjuvant TDB triggers Mincle-dependent IL-1 production to induce MyD88-dependent Th1/Th17 responses in vivo.

Arbitrary helicity control of circularly polarized light from lateral-type spin-polarized light-emitting diodes at room temperature

Science.gov (United States)

Nishizawa, Nozomi; Aoyama, Masaki; Roca, Ronel C.; Nishibayashi, Kazuhiro; Munekata, Hiro

2018-05-01

We demonstrate arbitrary helicity control of circularly polarized light (CPL) emitted at room temperature from the cleaved side facet of a lateral-type spin-polarized light-emitting diode (spin-LED) with two ferromagnetic electrodes in an antiparallel magnetization configuration. Driving alternate currents through the two electrodes results in polarization switching of CPL with frequencies up to 100 kHz. Furthermore, tuning the current density ratio in the two electrodes enables manipulation of the degree of circular polarization. These results demonstrate arbitrary electrical control of polarization with high speed, which is required for the practical use of lateral-type spin-LEDs as monolithic CPL light sources.

Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses.

Science.gov (United States)

Ye, Zi; Deng, Bolin; Wang, Chaokui; Zhang, Dike; Kijlstra, Aize; Yang, Peizeng

2016-02-04

Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses.

Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neo-Vascularization

Science.gov (United States)

Dubrac, Alexandre; Genet, Gael; Ola, Roxana; Zhang, Feng; Pibouin-Fragner, Laurence; Han, Jinah; Zhang, Jiasheng; Thomas, Jean-Léon; Chedotal, Alain; Schwartz, Martin A.; Eichmann, Anne

2015-01-01

Background Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2. Methods and Results Mice carrying inducible, endothelial-specific Nck1/2 deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of NCK1 and 2 inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for both Slit2 and VEGF induced front-rear polarity. Selective inhibition of polarized endothelial cell migration by targeting Nck1/2 prevents hypersprouting induced by Notch or Bmp signaling inhibition, as well as pathological ocular neovascularization and wound healing. Conclusions These data reveal a novel signal integration mechanism involving NCK1/2, ROBO1/2 and VEGFR2 that controls endothelial cell front-rear polarity during sprouting angiogenesis. PMID:26659946

Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma.

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Huang, T J; MacAry, P A; Eynott, P; Moussavi, A; Daniel, K C; Askenase, P W; Kemeny, D M; Chung, K F

2001-01-01

Th2 T cell immune-driven inflammation plays an important role in allergic asthma. We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia. OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge. Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA. Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 cells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma. Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.

Molecular networks linked by Moesin drive remodeling of the cell cortex during mitosis

Science.gov (United States)

Roubinet, Chantal; Decelle, Barbara; Chicanne, Gaëtan; Dorn, Jonas F.; Payrastre, Bernard; Payre, François; Carreno, Sébastien

2011-01-01

The cortical mechanisms that drive the series of mitotic cell shape transformations remain elusive. In this paper, we identify two novel networks that collectively control the dynamic reorganization of the mitotic cortex. We demonstrate that Moesin, an actin/membrane linker, integrates these two networks to synergize the cortical forces that drive mitotic cell shape transformations. We find that the Pp1-87B phosphatase restricts high Moesin activity to early mitosis and down-regulates Moesin at the polar cortex, after anaphase onset. Overactivation of Moesin at the polar cortex impairs cell elongation and thus cytokinesis, whereas a transient recruitment of Moesin is required to retract polar blebs that allow cortical relaxation and dissipation of intracellular pressure. This fine balance of Moesin activity is further adjusted by Skittles and Pten, two enzymes that locally produce phosphoinositol 4,5-bisphosphate and thereby, regulate Moesin cortical association. These complementary pathways provide a spatiotemporal framework to explain how the cell cortex is remodeled throughout cell division. PMID:21969469

Gluten-free diet does not influence the occurrence and the Th1/Th17-Th2 nature of immune-mediated diseases in patients with coeliac disease.

Science.gov (United States)

Imperatore, Nicola; Rispo, Antonio; Capone, Pietro; Donetto, Sara; De Palma, Giovanni Domenico; Gerbino, Nicolò; Rea, Matilde; Caporaso, Nicola; Tortora, Raffaella

2016-07-01

Coeliac disease (CD) is the most common Th1-mediated enteropathy, frequently associated with other immune-mediated disorders (IMD). To evaluate: (1) the prevalence of IMD at the time of and after CD diagnosis; (2) a possible change in immune response to gluten free diet (GFD); (3) the potential role of GFD in reducing and/or preventing IMD in CD. Prospective study including all consecutive adult CD patients who underwent investigations for Th1-Th17/Th2-IMD at the time of CD diagnosis and after a 5-year follow-up period. 1255 CD were enrolled. Of these, 257 patients (20.5%) showed IMD at the time of CD diagnosis, with 58.4% presenting a Th1/Th17-IMD. After a 5-year follow-up period, 682 patients (54.3%) showed new IMD despite GFD. Of these, 57.3% presented a Th1/Th17-IMD and 42.7% a Th2-IMD (p=0.8). When compared the prevalence of each type of IMD before and after CD diagnosis, we did not identify any significant "switch" from Th1/Th17- to Th2-IMD or vice versa. The number of patients with Th1/Th17- and/or Th2-IMD increased during the GFD period (20.5% vs 54.3%; p<0.01; OR 1.9). The prevalence of IMD at the time of CD diagnosis is high and it seems to increase in the follow-up period despite GFD. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

16th International Workshop on Polarized Sources, Targets, and Polarimetry (PSTP 2015)

CERN Document Server

2015-01-01

The Workshop on Polarized Sources, Targets and Polarimetry has been a tradition for more than 20 years, moving between Europe, USA and Japan. The XVIth International Workshop on Polarized Sources, Targets and Polarimetry (PSTP 2015) will take place at the Ruhr-University of Bochum, Germany. The workshop addresses the physics and technological challenges related to polarized gas/solid targets, polarized electron/positron/ion/neutron sources, polarimetry and their applications. will be published in Proceedings of Science

Th17 Immune Cells in vivo: Friend or Foe? | Center for Cancer Research

Science.gov (United States)

Upon encountering an antigen, T cells bearing CD4+ (a helper marker) proliferate and become polarized. During this process, the cells produce specific signaling molecules called cytokines.  This signaling stimulates the T cells to become more specialized.  What results is the production of T cell subsets such as Th1, Th17, or others.

MicroRNA-145 influences the balance of Th1/Th2 via regulating RUNX3 in asthma patients.

Science.gov (United States)

Fan, Linxia; Wang, Xiaojun; Fan, Linlan; Chen, Qizhang; Zhang, Hong; Pan, Hui; Xu, Aixia; Wang, Hongjuan; Yu, Yang

To delineate the underlying mechanism of microRNA-145 modulate the balance of Th1/Th2 via targeting RUNX3 in asthma patients. Peripheral blood samples were collected from asthma patients and healthy controls. CD4 + T cells were isolated and cultured. Using quantitative PCR detect, the level of microRNA-145 and RUNX3 mRNA level in the CD4 + T cells from asthma patients and healthy controls, meanwhile, western blot was used to detect the RUNX3 protein level. Th1 or Th2 related cytokines were measured by enzyme-linked immunosorbent assay. Dual-Luciferase Reporter Assay was performed to confirm the correlation between microRNA-145 and RUNX3. MicroRNA-145 mimic or inhibitor was transfected in the CD4 + T cells and the changes of RUNX3 level, Th1 or Th2 related cytokines and the percentage of Th1 and Th2 were observed after transfection. MicroRNA-145 level of CD4 + T cells was higher with a lower RUNX3 expression in asthma patients. There is negative correlation between microRNA-145 and RUNX3. Th2 hyperactivity and Th1 deficiency was detected in the CD4 + T cells of asthma patients. Dual-Luciferase Reporter Assay has shown that RUNX3 is a target of microRNA. Up-regulation or down-regulation of miR-145 level caused RUNX3 expression changes in CD4 + T cells and influence the related cytokines. Inhibition of microRNA-145 may reverse the imbalance of Th1/Th2 in asthma patients. MicroRNA-145 could regulate the balance of Th1/Th2 through targeting the RUNX3 in asthma patients. MicroRNA-145 and RUNX3 may be used as biomarkers or targets in the diagnosis or therapy of asthma.

Redundant Notch1 and Notch2 signaling is necessary for IFNγ secretion by T helper 1 cells during infection with Leishmania major.

Directory of Open Access Journals (Sweden)

Floriane Auderset

Full Text Available The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4(+ T helper (Th 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral CD4(+ T helper 1 cells is not well understood. Of the four Notch receptors, only Notch1 (N1 and Notch2 (N2 are expressed on activated CD4(+ T cells. To investigate the role of Notch in Th1 cell differentiation following parasite infection, mice with T cell-specific gene ablation of N1, N2 or both (N1N2(ΔCD4Cre were infected with the protozoan parasite Leishmania major. N1N2(ΔCD4Cre mice, on the C57BL/6 L. major-resistant genetic background, developed unhealing lesions and uncontrolled parasitemia. Susceptibility correlated with impaired secretion of IFNγ by draining lymph node CD4(+ T cells and increased secretion of the IL-5 and IL-13 Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were resistant to infection and developed a protective Th1 immune response, showing that CD4(+ T cell expression of N1 or N2 is redundant in driving Th1 differentiation. Furthermore, we show that Notch signaling is required for the secretion of IFNγ by Th1 cells. This effect is independent of CSL/RBP-Jκ, the major effector of Notch receptors, since L. major-infected mice with a RBP-Jκ deletion in their T cells were able to develop IFNγ-secreting Th1 cells, kill parasites and heal their lesions. Collectively, we demonstrate here a crucial role for RBP-Jκ-independent Notch signaling in the differentiation of a functional Th1 immune response following L. major infection.

Targeting beta- and alpha-adrenergic receptors differentially shifts Th1, Th2, and inflammatory cytokine profiles in immune organs to attenuate adjuvant arthritis

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Dianne eLorton

2014-08-01

Full Text Available The sympathetic nervous system (SNS regulates host defense responses and restores homeostasis. SNS-immune regulation is altered in rheumatoid arthritis (RA and rodent models of RA, characterized by nerve remodeling in immune organs and defective adrenergic receptor (AR signaling to immune cell targets that typically promotes or suppresses inflammation via α- and β2-AR activation, respectively, and indirectly drives humoral immunity by blocking Th1 cytokine secretion. Here, we investigate how β2-AR stimulation and/or α-AR blockade at disease onset affects disease pathology and cytokine profiles in relevant immune organs from male Lewis rats with adjuvant-induced arthritis (AA. Rats challenged to induce AA were treated with terbutaline (TERB, a β2-AR agonist (600 μg/kg/day and/or phentolamine (PHEN, an α-AR antagonist (5.0 mg/kg/day or vehicle from disease onset through severe disease. We report that in spleen, mesenteric (MLN and draining lymph node (DLN cells, TERB reduces proliferation, an effect independent of IL-2. TERB also fails to shift Th cytokines from a Th1 to Th2 profile in spleen and MLN (no effect on IFN-γ and DLN (greater IFN-γ cells. In splenocytes, TERB, PHEN and co-treatment (PT promotes an anti-inflammatory profile (greater IL-10 and lowers TNF-α (PT only. In DLN cells, drug treatments do not affect inflammatory profiles, except PT, which raised IL-10. In MLN cells, TERB or PHEN lowers MLN cell secretion of TNF-α or IL-10, respectively. Collectively, our findings indicate disrupted β2-AR, but not α-AR signaling in AA. Aberrant β2-AR signaling consequently derails the sympathetic regulation of lymphocyte expansion, Th cell differentiation, and inflammation in the spleen, DLNs and MLNs that is required for immune system homeostasis. Importantly, this study provides potential mechanisms through which reestablished balance between α- and β2-AR function in the immune system ameliorates inflammation and joint

Atmospheric Polarization Imaging with Variable Aerosols, Clouds, and Surface Albedo

Science.gov (United States)

2013-07-01

values found in this region only during episodes of intense wildfire smoke. Detailed analysis of the aerosols in this smoke plume and their effect...Continuous outdoor operation of an all-sky polarization imager,” Proc. SPIE 7672 (Polarization: Measurement, Analysis , and Remote Sensing IX), 76720A-1-7, 7...Pust, “ Lunar corona in ice wave cloud,” 10th International Meeting on Light and Color in Nature, St. Mary’s College of Maryland, 16-20 June 2010. 2

Treatment in vitro with PPARα and PPARγ ligands drives M1-to-M2 polarization of macrophages from T. cruzi-infected mice.

Science.gov (United States)

Penas, Federico; Mirkin, Gerardo A; Vera, Marcela; Cevey, Ágata; González, Cintia D; Gómez, Marisa I; Sales, María Elena; Goren, Nora B

2015-05-01

Trypanosoma cruzi, the etiological agent of Chagas' disease, induces a persistent inflammatory response. Macrophages are a first line cell phenotype involved in the clearance of infection. Upon parasite uptake, these cells increase inflammatory mediators like NO, TNF-α, IL-1β and IL-6, leading to parasite killing. Although desired, inflammatory response perpetuation and exacerbation may lead to tissue damage. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors that, besides regulating lipid and carbohydrate metabolism, have a significant anti-inflammatory effect. This is mediated through the interaction of the receptors with their ligands. PPARγ, one of the PPAR isoforms, has been implicated in macrophage polarization from M1, the classically activated phenotype, to M2, the alternatively activated phenotype, in different models of metabolic disorders and infection. In this study, we show for the first time that, besides PPARγ, PPARα is also involved in the in vitro polarization of macrophages isolated from T. cruzi-infected mice. Polarization was evidenced by a decrease in the expression of NOS2 and proinflammatory cytokines and the increase in M2 markers like Arginase I, Ym1, mannose receptor and TGF-β. Besides, macrophage phagocytic activity was significantly enhanced, leading to increased parasite load. We suggest that modulation of the inflammatory response by both PPARs might be due, at least in part, to a change in the profile of inflammatory macrophages. The potential use of PPAR agonists as modulators of overt inflammatory response during the course of Chagas' disease deserves further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

POLARIZED BEAMS: 1 - Longitudinal electron spin polarization at HERA

Energy Technology Data Exchange (ETDEWEB)

Anon.

1994-09-15

Wednesday 4 May marked a turning point in the art of the manipulation of spins in electron storage rings: longitudinal electron spin polarization (with the spins oriented along the electrons' direction of motion) was established in the electron ring of HERA, the electronproton collider at DESY in Hamburg. A polarization level of about 55% was obtained and polarizations of over 60% were reproducibly obtained in the following days. The beam energy was 27.52 GeV, corresponding to half integer spin tune of 62.5.

Mass dependence of azimuthal asymmetry in the fission of 232Th and 233,235,236,238U by polarized photons

International Nuclear Information System (INIS)

Denyak, V.V.; Khvastunov, V.M.; Paschuk, S.A.; Schelin, H.R.

2013-01-01

Fission of the even-even nuclei 232 Th, 236,238 U and even-odd nuclei 233,235 U by linearly polarized photons has been studied at excitation energies in the region of a giant dipole resonance. The performed investigations unambiguously showed the existence of the fragment mass dependence of the cross section azimuthal asymmetry in the photofission of 236 U and 238 U. In addition, the obtained results provided the first evidence for the possible difference between the asymmetry values in asymmetric and symmetric mass distribution regions in the case of 236 U. The measured cross section azimuthal asymmetry of the fission of 232 Th does not show any fragment mass dependence. In the even-odd nuclei 233 U and 235 U the difference between the far-asymmetric and other mass distribution regions was also observed but with the statistical uncertainty not small enough for definitive conclusion. (orig.)

Opportunity's View After Drive on Sol 1806

Science.gov (United States)

2009-01-01

NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 60.86 meters (200 feet) on the 1,806th Martian day, or sol, of Opportunity's surface mission (Feb. 21, 2009). North is at the center; south at both ends. Tracks from the drive extend northward across dark-toned sand ripples and light-toned patches of exposed bedrock in the Meridiani Planum region of Mars. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). Engineers designed the Sol 1806 drive to be driven backwards as a strategy to redistribute lubricant in the rovers wheels. The right-front wheel had been showing signs of increased friction. The rover's position after the Sol 1806 drive was about 2 kilometer (1.2 miles) south southwest of Victoria Crater. Cumulative odometry was 14.74 kilometers (9.16 miles) since landing in January 2004, including 2.96 kilometers (1.84 miles) since climbing out of Victoria Crater on the west side of the crater on Sol 1634 (August 28, 2008). This view is presented as a cylindrical projection with geometric seam correction.

Aberrant Production of Th1/Th2/Th17-Related Cytokines in Serum of C57BL/6 Mice after Short-Term Formaldehyde Exposure

Directory of Open Access Journals (Sweden)

Haiyan Wei

2014-09-01

Full Text Available Previous studies have shown that formaldehyde (FA could cause immunotoxicity by changing the number of T lymphocytes and that cytokines play a pivotal role in the regulation of T lymphocytes. However, the previously used cytokine detection methods are difficult to use in the measurement of several cytokines in a small amount of sample for one test. Therefore, the cytometric bead array (CBA technique was used. CBA showed better analytical efficiency and sensitivity than the previous methods. C57BL/6 mice were exposed to the control (normal saline, low FA concentration (0.5 mg/kg, and high FA concentration (2 mg/kg for 1 week or 1 month. The contents of cytokines, including Th1-related cytokines (IL-2, IFN-γ, and tumor necrosis factor, Th2-related cytokines (IL-4, IL-6, and IL-10, and Th17-related cytokines (IL-17A, were measured by using the BD FACS Canto II Flow Cytometer and analyzed by FCAP ArrayTM Software. Th1/Th2/Th17-related cytokines showed a slightly decreasing trend after low FA exposure. Conversely, a significantly increasing trend was found after high FA exposure. Th1/Th2/Th17-related cytokines all serve important functions in the immune reactions in mice after FA exposure.

Wind-Sculpted Vicinity After Opportunity's Sol 1797 Drive

Science.gov (United States)

2009-01-01

NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 111 meters (364 feet) on the 1,797th Martian day, or sol, of Opportunity's surface mission (Feb. 12, 2009). North is at the center; south at both ends. Tracks from the drive recede northward across dark-toned sand ripples in the Meridiani Planum region of Mars. Patches of lighter-toned bedrock are visible on the left and right sides of the image. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). This view is presented as a cylindrical projection with geometric seam correction.

Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

DEFF Research Database (Denmark)

Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank

2013-01-01

'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months...... in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained...... changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses. © 2013 S. Karger AG, Basel....

Multiparameter fluorescence imaging for quantification of TH-1 and TH-2 cytokines at the single-cell level

Science.gov (United States)

Fekkar, Hakim; Benbernou, N.; Esnault, S.; Shin, H. C.; Guenounou, Moncef

1998-04-01

Immune responses are strongly influenced by the cytokines following antigenic stimulation. Distinct cytokine-producing T cell subsets are well known to play a major role in immune responses and to be differentially regulated during immunological disorders, although the characterization and quantification of the TH-1/TH-2 cytokine pattern in T cells remained not clearly defined. Expression of cytokines by T lymphocytes is a highly balanced process, involving stimulatory and inhibitory intracellular signaling pathways. The aim of this study was (1) to quantify the cytokine expression in T cells at the single cell level using optical imaging, (2) and to analyze the influence of cyclic AMP- dependent signal transduction pathway in the balance between the TH-1 and TH-2 cytokine profile. We attempted to study several cytokines (IL-2, IFN-(gamma) , IL-4, IL-10 and IL-13) in peripheral blood mononuclear cells. Cells were prestimulated in vitro using phytohemagglutinin and phorbol ester for 36h, and then further cultured for 8h in the presence of monensin. Cells were permeabilized and then simple-, double- or triple-labeled with the corresponding specific fluorescent monoclonal antibodies. The cell phenotype was also determined by analyzing the expression of each of CD4, CD8, CD45RO and CD45RA with the cytokine expression. Conventional images of cells were recorded with a Peltier- cooled CCD camera (B/W C5985, Hamamatsu photonics) through an inverted microscope equipped with epi-fluorescence (Diaphot 300, Nikon). Images were digitalized using an acquisition video interface (Oculus TCX Coreco) in 762 by 570 pixels coded in 8 bits (256 gray levels), and analyzed thereafter in an IBM PC computer based on an intel pentium processor with an adequate software (Visilog 4, Noesis). The first image processing step is the extraction of cell areas using an edge detection and a binary thresholding method. In order to reduce the background noise of fluorescence, we performed an opening

Associations between parenting styles and teen driving, safety-related behaviors and attitudes.

Science.gov (United States)

Ginsburg, Kenneth R; Durbin, Dennis R; García-España, J Felipe; Kalicka, Ewa A; Winston, Flaura K

2009-10-01

The goal was to explore the association between parenting style and driving behaviors. The 2006 National Young Driver Survey gathered data on driving safety behaviors from a nationally representative sample of 5665 ninth-, 10th-, and 11th-graders. A parenting style variable was based on adolescent reports and separated parents into 4 groups, (1) authoritative (high support and high rules/monitoring), (2) authoritarian (low support and high rules/monitoring), (3) permissive (high support and low rules/monitoring), and (4) uninvolved (low support and low rules/monitoring). Associations between parenting style and driving behaviors and attitudes were assessed. One half of parents were described as authoritative, 23% as permissive, 8% as authoritarian, and 19% as uninvolved. Compared with teens with uninvolved parents, those with authoritative parents reported one half the crash risk in the past year (odds ratio [OR]: 0.47 [95% confidence interval [CI]: 0.26-0.87]), were 71% less likely to drive when intoxicated (OR: 0.29 [95% CI: 0.19-0.44]), and were less likely to use a cellular telephone while driving (OR: 0.71 [95% CI: 0.50-0.99]). Teens with authoritative or authoritarian parents reported using seat belts nearly twice as often (authoritative: OR: 1.94 [95% CI: 1.49 -2.54]; authoritarian: OR: 1.85 [95% CI: 1.08 -3.18]) and speeding one half as often (authoritative: OR: 0.47 [95% CI: 0.36-0.61]; authoritarian: OR: 0.63 [95% CI: 0.40-0.99]) as teens with uninvolved parents. No significant differences in crash risk or seat belt use were found between permissive and uninvolved parents. Clinicians should encourage parents to set rules and to monitor teens' driving behaviors, in a supportive context.

Shear-wave polarization analysis of the seismic swarm following the July 9th 1998 Faial (Azores) earthquake

Science.gov (United States)

Dias, N. A.; Matias, L.; Tellez, J.; Senos, L.; Gaspar, J. L.

2003-04-01

The Azores Islands, located at a tectonic triple Junction, geodynamically are a highly active place. The seismicity in this region occurs mainly in the form of two types of seismic swarms with tectonic and/or volcanic origins, lasting from hours to years. In some cases the swarm follows a main stronger shock, while in others the more energetic event occurs sometime after the beginning of the swarm. In order to understand the complex phenomena of this region, a multidisciplinary approach is needed, involving geophysical, geological and geochemical studies such as the one being carried under the MASHA project (POCTI/CTA/39158/2001), On July 9th 1998 an Mw=6.2 earthquake stroked the island of Faial, in the central group of the Azores archipelago, followed by a seismic swarm still active today. We will present some preliminary results of the shear-wave polarization analysis of a selected dataset of events of this swarm. These correspond to the 112 best- constrained events, record during the first 2 weeks by the seismic network deployed on the 3 islands surrounding the area of the main shock. The objective was to analyse the behaviour of the S wave polarization and the eventual relationship with the presence of seismic anisotropy under the seismic stations, and to correlate this with the regional structure and origin of the Azores plateau. Two main tectonic features are observable on the islands, one primarily orientated SE-NW and the other crossing it roughly with the WNW-ESE direction. The polarization direction observed in the majority of the seismic stations is not stable, varying from SE-NW to WSW-ENE, and showing also the presence in same cases of shear-wave splitting, indicating the presence of anisotropy. Part of the polarization seems to be coherent with the direction of the local tectonic features, but its instability suggest a more complex seismic anisotropy than that proposed by the model EDA of Crampin. Furthermore, the dataset revealed some limitations to

Neoclassical effects on RF current drive in tokamaks

International Nuclear Information System (INIS)

Yoshioka, K.; Antonsen, T.M. Jr.

1986-01-01

Neoclassical effects on RF current drive which arise because of the inhomogeneity of the magnetic field in tokamak devices are analysed. A bounce averaged 2-D Fokker-Planck equation is derived from the drift kinetic equation and is solved numerically. The model features current drive due to a strong RF wave field. The efficiency of current drive by electron cyclotron waves is significantly reduced when the waves are absorbed at the low magnetic field side of a given flux surface, whereas the efficiency remains at the same level as in the homogeneous ideal plasma when the waves are absorbed at the high field side. The efficiency of current drive by fast waves (compressional Alfven waves) with low phase velocity (vsub(parallel)/vsub(th)<1) is significantly degraded by neoclassical effects, no matter where the wave is absorbed, and the applicability of this wave seems, therefore, to be doubtful. (author)

Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritis.

Science.gov (United States)

Lin, Jinpiao; Xiao, Lianbo; Ouyang, Guilin; Shen, Yu; Huo, Rongfen; Zhou, Zhou; Sun, Yue; Zhu, Xianjin; Zhang, Jie; Shen, Baihua; Li, Ningli

2012-12-01

Total glucoside of paeony (TGP), an active compound extracted from paeony root, has been used in therapy for rheumatoid arthritis (RA). Th1 and Th17 cells are now believed to play crucial roles in the lesions of RA. However, the molecular mechanism of TGP in inhibition of Th1 and Th17 cells remains unclear. In this study, we found that TGP treatment significantly decreased percentage and number of Th1 and Th17 cells in collagen induced arthritis (CIA) mice. Consistently, treatment with TGP decreased expression of T-bet and RORγt as well as phosphorylation of STAT1 and STAT3. In particular, TGP treatment inhibited dendritic cells (DCs) maturation and reduced production of IL-12 and IL-6. Moreover, TGP-treatment RA patients showed shank population of matured DCs and IFN-γ-, IL-17-producing cells. Taken together, our results demonstrated that TGP inhibited maturation and activation of DCs, which led to impaired Th1 and Th17 differentiation in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

Cigarette Smoke Induction of Interleukin-27/WSX-1 Regulates the Differentiation of Th1 and Th17 Cells in a Smoking Mouse Model of Emphysema.

Science.gov (United States)

Qiu, Shi-Lin; Duan, Min-Chao; Liang, Yi; Tang, Hai-Juan; Liu, Guang-Nan; Zhang, Liang-Ming; Yang, Chao-Mian

2016-01-01

IFN-γ-producing CD4 + T (Th1) cells and IL-17-producing CD4 + T (Th17) cells play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immune regulation between Th1 and Th17 cells remains unclear. Previous studies have demonstrated that interleukin-27 (IL-27)/WSX-1 exerted pro- or anti-inflammatory effects in many acute inflammatory diseases by modulating T cell-mediated immune response, but little was known about its role in chronic inflammatory disease, especially in smoking-related lung diseases. Considering IL-27 is an important regulator in T lymphocytes immune responses and was found markedly increased in patients with COPD, we hypothesized that IL-27/WSX-1 may exert immuno-regulatory effects on the differentiation of Th1 and Th17 cells in smoking-related COPD. In this study, we aimed to evaluate the expression of IL-27 in patients with COPD and explore the role of IL-27/WSX-1 on Th1 and Th17 cells differentiation in a smoking mouse model of emphysema. We found that elevated expression of IL-27 was associated with increased proportion of Th1 cells and Th17 cells in patients with COPD and demonstrated parallel findings in cigarette smoke-exposed mice. In addition, cigarette smoke exposure upregulated the expression of IL-27R (WSX-1) by naive CD4 + T cells in mice. In vitro , IL-27 significantly augmented the secretion of IFN-γ by naive CD4 + T cells via a T-bet, p-STAT1, and p-STAT3-dependent manner, but inhibited the production of IL-17 by a ROR-γt and p-STAT1-dependent way. Furthermore, anti-IL27 treatment dramatically decreased the expression of IFN-γ-producing CD4 + T cells in cigarette smoke-exposed mice. These findings proposed that IL-27 has functions for promoting the expression of Th1 cells but inhibiting the expression of Th17 cells in vitro and IL-27 neutralization-attenuated Th1-mediated inflammation in vivo , suggesting targeting IL-27/WSX-1 may provide a new therapeutic approach for smoking

Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program

Science.gov (United States)

Brown, Chrysothemis C.; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M.; Noelle, Randolph J.

2015-01-01

Summary CD4+ T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. PMID:25769610

Th1 and Th17 Cells and Associated Cytokines Discriminate among Clinically Isolated Syndrome and Multiple Sclerosis Phenotypes.

Science.gov (United States)

Arellano, Gabriel; Acuña, Eric; Reyes, Lilian I; Ottum, Payton A; De Sarno, Patrizia; Villarroel, Luis; Ciampi, Ethel; Uribe-San Martín, Reinaldo; Cárcamo, Claudia; Naves, Rodrigo

2017-01-01

Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. It is a heterogeneous pathology that can follow different clinical courses, and the mechanisms that underlie the progression of the immune response across MS subtypes remain incompletely understood. Here, we aimed to determine differences in the immunological status among different MS clinical subtypes. Blood samples from untreated patients diagnosed with clinically isolated syndrome (CIS) ( n  = 21), different clinical forms of MS ( n  = 62) [relapsing-remitting (RRMS), secondary progressive, and primary progressive], and healthy controls (HCs) ( n  = 17) were tested for plasma levels of interferon (IFN)-γ, IL-10, TGF-β, IL-17A, and IL-17F by immunoanalysis. Th1 and Th17 lymphocyte frequencies were determined by flow cytometry. Our results showed that IFN-γ levels and the IFN-γ/IL-10 ratio were higher in CIS patients than in RRMS patients and HC. Th1 cell frequencies were higher in CIS and RRMS than in progressive MS, and RRMS had a higher Th17 frequency than CIS. The Th1/Th17 cell ratio was skewed toward Th1 in CIS compared to MS phenotypes and HC. Receiver operating characteristic statistical analysis determined that IFN-γ, the IFN-γ/IL-10 ratio, Th1 cell frequency, and the Th1/Th17 cell ratio discriminated among CIS and MS subtypes. A subanalysis among patients expressing high IL-17F levels showed that IL-17F and the IFN-γ/IL-17F ratio discriminated between disease subtypes. Overall, our data showed that CIS and MS phenotypes displayed distinct Th1- and Th17-related cytokines and cell profiles and that these immune parameters discriminated between clinical forms. Upon validation, these parameters might be useful as biomarkers to predict disease progression.

Impaired Gal-9 Dysregulates the PBMC-Induced Th1/Th2 Imbalance in Abortion-Prone Matings

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Mengzhou He

2018-01-01

Full Text Available Recurrent miscarriage is defined as the loss of 3 or more consecutive pregnancies; however, the underlying immunologic mechanisms that trigger pregnancy loss remain largely unelucidated. Galectin-9 (Gal-9 may modulate a variety of biologic functions and play an important role in Th1/Th2 immune deviation. To analyze the mechanism of Gal-9 in abortion, we used the classical abortion-prone mouse model (DBA/2-mated CBA/J mice to detect the expression of Gal-9 at the maternal-fetal interface. We also mimicked the immune environment of pregnancy by culturing trophoblast cells with peripheral blood mononuclear cells (PBMCs to explore how Gal-9 might be involved in the pathogenesis of abortion. We found that the expression levels of Gal-9 in abortion-prone matings were lower than that for controls. Using a coculture system, we detected a Th1 preponderance in the coculture from abortion-prone matings. Furthermore, Gal-9 blockade augmented the imbalance of Th1/Th2 immunity in abortion-prone matings by promoting the secretion of Th1-derived cytokines in coculture, while there was a Th2 preponderance when we administered recombinant Gal-9. In conclusion, our results suggest that the Gal-9 signal is important for the regulation of PBMC function toward a Th2 bias at the maternal-fetal interface, which is beneficial for the maintenance of a normal pregnancy.

The expanding universe of T-cell subsets: Th1, Th2 and more.

Science.gov (United States)

Mosmann, T R; Sad, S

1996-03-01

Since their discovery nearly ten years ago, T helper 1 (Th1) and Th2 subsets have been implicated in the regulation of many immune responses. In this article, Tim Mosmann and Subash Sad discuss the increasing number of T-cell subsets defined by cytokine patterns; the differentiation pathways of CD4+ and CD8+ T cells; the contribution of other cell types to these patterns; and the cytokine interactions during infection and pregnancy.

Effect of Nonlocal Electron Transport in Both Directions on the Symmetry of Polar-Drive--Ignition Targets

Science.gov (United States)

Delettrez, J. A.; Collins, T. J. B.; Shvydky, A.; Moses, G.; Cao, D.; Marinak, M. M.

2012-10-01

A nonlocal, multigroup diffusion model for thermal electron transportfootnotetextG. P. Schurtz, Ph. D. Nicola"i, and M. Busquet, Phys. Plasmas 7, 4238 (2000). has been added to the 2-D hydrodynamic code DRACO. This model has been applied to simulations of polar-drive (PD) NIF ignition designs. Previous simulations were carried out with a constant flux-limiter model in both the radial and transverse directions. Due to the nonsymmetry of PD illumination, these implosions suffer from low-mode nonuniformities that affect their performance. Nonlocal electron transport in both directions is expected to reduce these nonuniformities. The 2-D thermal electron flux from simulations, using either the nonlocal model or the standard flux-limited approach, will be compared and the effect of the nonlocal transport model on the growth of the nonuniformities and on target performance will be presented. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302.

Change of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion

Institute of Scientific and Technical Information of China (English)

Shi-Hua Zhou

2016-01-01

Objective:To analyze and investigate the change state of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion. Methods: A total of 92 patients with recurrent spontaneous abortion in our hospital from June 2013 to July 2015 were selected as the observation group and 92 women with health delivery history at the same time were selected as the control group,then the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of two groups were detected and compared and the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of patients with different gestational age at abortion and abortion times were compared too. Results:The peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of observation group and control group all had obvious differences,and those blood indexes levels' differences of patients with different gestational age at abortion and abortion times were obvious too, all P<0.05 and the differences were significant. Conclusions: The T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion show abnormal state and the differences of detection results of patients with different gestational age at abortion and abortion times are relatively obvious,so those indexes should be monitored and improved intentinonally.

Common Features of Regulatory T Cell Specialization During Th1 Responses

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Katharina Littringer

2018-06-01

Full Text Available CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 immune responses, co-expression of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to control Th1 responses. T-bet-dependent expression of CXCR3 directs Treg cells to the site of inflammation. However, the suppressive mediators enabling effective control of Th1 responses at this site are unknown. In this study, we determined the signature of CXCR3+ Treg cells arising in Th1 settings and defined universal features of Treg cells in this context using multiple Th1-dominated infection models. Our analysis defined a set of Th1-specific co-inhibitory receptors and cytotoxic molecules that are specifically expressed in Treg cells during Th1 immune responses in mice and humans. Among these, we identified the novel co-inhibitory receptor CD85k as a functional predictor for Treg-mediated suppression specifically of Th1 responses, which could be explored therapeutically for selective immune suppression in autoimmunity.

Polarized targets in high energy physics

Energy Technology Data Exchange (ETDEWEB)

Cates, G.D. Jr. [Princeton Univ., NJ (United States)

1994-12-01

Various approaches are discussed for producing polarized nuclear targets for high energy physics experiments. As a unifying theme, examples are drawn from experiments to measure spin dependent structure functions of nucleons in deep inelastic scattering. This single physics goal has, over roughly two decades, been a driving force in advances in target technology. Actual or planned approaches have included solid targets polarized by dynamic nuclear polarization (DNP), several types of internal targets for use in storage rings, and gaseous {sup 3}He targets polarized by spin-exchange optical pumping. This last approach is the type of target adopted for SLAC E-142, an experiment to measure the spin structure function of the neutron, and is described in detail.

Polarized targets in high energy physics

International Nuclear Information System (INIS)

Cates, G.D. Jr.

1994-01-01

Various approaches are discussed for producing polarized nuclear targets for high energy physics experiments. As a unifying theme, examples are drawn from experiments to measure spin dependent structure functions of nucleons in deep inelastic scattering. This single physics goal has, over roughly two decades, been a driving force in advances in target technology. Actual or planned approaches have included solid targets polarized by dynamic nuclear polarization (DNP), several types of internal targets for use in storage rings, and gaseous 3 He targets polarized by spin-exchange optical pumping. This last approach is the type of target adopted for SLAC E-142, an experiment to measure the spin structure function of the neutron, and is described in detail

1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H17 cells to protect against experimental autoimmune encephalomyelitis.

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Jae-Hoon Chang

Full Text Available BACKGROUND: Vitamin D(3, the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D(3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE; however, the direct effect of vitamin D(3 on T cells is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In an in vitro system using cells from mice, the active form of vitamin D(3 (1,25-dihydroxyvitamin D(3 suppresses both interleukin (IL-17-producing T cells (T(H17 and regulatory T cells (Treg differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D(3 (1,25(OH(2D(3 to reduce the amount of IL-2 regulates the generation of Treg cells, but not T(H17 cells. Under T(H17-polarizing conditions, 1,25(OH(2D(3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH(2D(3's negative regulation of T(H17 development is still defined in the IL-10(-/- T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH(2D(3 inhibits IL-17 production in STAT1(-/- T cells. Most interestingly, 1,25(OH(2D(3 negatively regulates CCR6 expression which might be essential for T(H17 cells to enter the central nervous system and initiate EAE. CONCLUSIONS/SIGNIFICANCE: Our present results in an experimental murine model suggest that 1,25(OH(2D(3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T(H17-mediated autoimmune diseases.

Extended driving impairs nocturnal driving performances.

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Patricia Sagaspe

Full Text Available Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3-5 am, 1-5 am and 9 pm-5 am on open highway. Fourteen young healthy men (mean age [+/-SD] = 23.4 [+/-1.7] years participated Inappropriate line crossings (ILC in the last hour of driving of each session, sleep variables, self-perceived fatigue and sleepiness were measured. Compared to the short (3-5 am driving session, the incidence rate ratio of inappropriate line crossings increased by 2.6 (95% CI, 1.1 to 6.0; P<.05 for the intermediate (1-5 am driving session and by 4.0 (CI, 1.7 to 9.4; P<.001 for the long (9 pm-5 am driving session. Compared to the reference session (9-10 pm, the incidence rate ratio of inappropriate line crossings were 6.0 (95% CI, 2.3 to 15.5; P<.001, 15.4 (CI, 4.6 to 51.5; P<.001 and 24.3 (CI, 7.4 to 79.5; P<.001, respectively, for the three different durations of driving. Self-rated fatigue and sleepiness scores were both positively correlated to driving impairment in the intermediate and long duration sessions (P<.05 and increased significantly during the nocturnal driving sessions compared to the reference session (P<.01. At night, extended driving impairs driving performances and therefore should be limited.

Changes of lymphocytes in spleen and liver by local irradiation to the maxilla in mice. Th1/Th2 balance

International Nuclear Information System (INIS)

Tamazawa, Ken; Satoh, Daigo; Yosue, Takashi

2001-01-01

This study was to examine changes in cell-mediated immunity by local irradiation, in particular focusing on the Th1/Th2 balance. We investigated influence due to local irradiation (10 Gy) of a portion of the maxilla in mice. The wet-weight of spleen, the percentage and the absolute numbers of the lymphocytes in spleen, wet-weight of the liver, the percentage of lymphocytes in liver were measured using a flow cytometer and values were compared with those obtained from non-irradiated animals. Furthermore, we analysed the percentage and absolute numbers of T helper 1 (Th1) cells, T cytotoxic 1 (Tc1) cells by the intracellular cytokine. The following results were obtained: Wet-weight of the spleen showed a significant decrease one and three days after irradiation. Wet-weight of the liver did not show any significant change after irradiation. In spleen, the percentage of Th1-like cells showed a significant increase one and three days after irradiation, and one of the Th2-like cells showed a significant decrease one day after irradiation. The ratio of the Th1-like cells to Th2-like cells showed an extreme increase one and three days after irradiation. The absolute numbers of the Th1-like cells and the Th2-like cells showed a significant decrease one and three days after irradiation. In liver, the percentage of the Th1-like cells showed a significant increase one and three days after irradiation, and the percentage of the Th2-like cells did not show any significant change after irradiation. The ratio of the Th1-like cells to Th2-like cells showed a significant increase one day after irradiation. In spleen, the percentage of the Th1 cells and Tc1 cells showed a significant increase one and three days after irradiation, but neither of the absolute numbers showed any significant change after irradiation. These results indicated that the characteristic changes of Th1/Th2 balance shifted to a Th1-dominant status by irradiation, and the ability from irradiation therapy to the

Radioimmunoassays of tetrahydroaldosterone (TH-Aldo) in human urine

International Nuclear Information System (INIS)

Kohl, K.-H.; Vecsei, P.; Abdelhamid, S.

1978-01-01

Specific antisera against tetrahydroaldosterone (TH-Aldo) were raised in two white New Zealand rabbits. 3α,5β-TH-aldo-20-oxime-bovine-serum albumin commplex was used as antigen. The resulting titers were 1:18 000 and 1:16 000. Except tetrahydrocortisol (THF) (0.23%) and tetrahydro-18-hydroxy-11-dehydrocorticosterone (18-OH-THA) (3.2%), all steroids and steroid metabolites gave negligible cross-reactions. Immunograms of the paper chromatograms made from the n-butanol-extract of the urines, as well as after β-glucuronidase treatment and dichlormethane extraction, were studied to further define the specificity of the antiserum. Antibody H 1 (used in this study) reacted with aldosterone-18-gluc., a TH-aldosterone-glucuronide (probably the 21-glucuronide) and an unidentified less polar material. Two methods were developed: a) TH-Aldo-glucuronide(s) estimation after ethylacetate pre-extraction as a rapid screening test of endogenous aldosterone production. b) estimation of TH-aldosterone using one chromatographic system. The results of method a) showed a significant correlation with the values obtained by technique b). Normal values (method b) were 25.88 plus minus 16.50 μg/24 h (range 9.5 - 64.8 μg/24 h). A significant correlation was also shown between the TH-aldo (technique b) and 18-gluc. values. (author)

Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.

Science.gov (United States)

Brown, Chrysothemis C; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; Al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M; Noelle, Randolph J

2015-03-17

CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Fasciola hepatica reinfection potentiates a mixed Th1/Th2/Th17/Treg response and correlates with the clinical phenotypes of anemia

Science.gov (United States)

Perez-Crespo, Ignacio; Chillón-Marinas, Carlos; Khoubbane, Messaoud; Quesada, Carla; Reguera-Gomez, Marta; Mas-Coma, Santiago; Fresno, Manuel; Gironès, Núria

2017-01-01

Background Fascioliasis is a severe zoonotic disease of worldwide extension caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm and anemia is the main sign. Herein, the profile of the Th1/Th2/Th17/Treg expression levels is analyzed after reinfection, correlating them with their corresponding hematological biomarkers of morbidity. Methodology/Principal findings The experimental design reproduces the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 8 weeks (R8), and at 12 weeks (R12), and negative control rats. In a cross-sectional study, the expression of the genes associated with Th1 (Ifng, Il12a, Il12b, Nos2), Th2 (Il4, Arg1), Treg (Foxp3, Il10, Tgfb, Ebi3), and Th17 (Il17) in the spleen and thymus was analyzed. After 20 weeks of primary infection, PI did not present significant changes in the expression of those genes when compared to non-infected rats (NI), but an increase of Il4, Arg1 and Ifng mRNA in the spleen was observed in R12, suggesting the existence of an active mixed Th1/Th2 systemic immune response in reinfection. Foxp3, Il10, Tgfb and Ebi3 levels increased in the spleen in R12 when compared to NI and PI, indicating that the Treg gene expression levels are potentiated in chronic phase reinfection. Il17 gene expression levels in R12 in the spleen increased when compared to NI, PI and R8. Gene expression levels of Il10 in the thymus increased when compared to NI and PI in R12. Ifng expression levels in the thymus increased in all reinfected rats, but not in PI. The clinical phenotype was determined by the fluke burden, the rat body weight and the hemogram. Multivariate mathematical models were built to describe the Th1/Th2/Th17/Treg expression levels and the clinical phenotype. In reinfection, two phenotypic patterns were detected: i) one which includes only increased splenic Ifng

Radioimmunological determination of tetrahydroaldosterone (TH-ALDO) in human urine

International Nuclear Information System (INIS)

Kohl, K.H.

1979-01-01

Two white New Zealand rabbits were immunised against TH-Aldo. A 3α. 5β-TH-Aldo-20 oxime BSA complex served as antigen. The titration values found were between 1:16.000 and 1:18.000. All steroids and steroid metabolites with the exception of tetra-hydro-18-hydroxy-11-dehydrocorticosterone (18-OH-THA) exhibited insignifcant slight cross-reactions. The specifity of the antisera was also investigated with immunograms using paper chromatography which was developed from the n-butanol extract of the urine samples as well as after β-glucuronida treatment and dichloromethane extraction. The immunogram showed that the antibodies crossreacted with aldosterone-18-glucuronide and with tetrahydroaldosterone-glucuronide fraction (possibly with the TH-Aldo-21-glucuronide) as well as with a non-identified weakly polar material. (orig./AJ) [de

Th1 and Th2 immune responses related to pelvic endometriosis Resposta imunológica Th1 e Th2 relacionada à endometriose pélvica

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Sergio Podgaec

2010-01-01

Full Text Available OBJECTIVE: This study analyzed the relationship between clinical characteristics of endometriosis and Th1/Th2 immune response patterns. METHODS: A prospective study was performed with 65 patients with endometriosis (Group A and 33 without the disease (Group B. Measurement of IL 2, 4 and 10, TNF-alpha and IFN-gamma was carried out in peripheral blood and peritoneal fluid. RESULTS: Serum TNF-alpha was higher in patients with endometriosis who had deep dyspareunia compared to controls (mean 4.5 pg/ml and 2.3 pg/ml, pOBJETIVO: Este estudo analisa a relação entre as características clínicas da endometriose e os padrões da resposta imune Th1/Th2. MÉTODOS: Estudo prospectivo realizado com 65 pacientes com endometriose (Grupo A e 33 pacientes sem a doença (Grupo B. Foram realizadas avaliação no fluido peritoneal e sangue periférico de IL 2, 4 e 10, TNF-alfa e IFN-gama. A significância foi estabelecida em p < 0,05. RESULTADOS: TNF-alfa encontrava-se elevado em pacientes com endometriose que apresentavam dispareunia de profundidade comparado com controle (média 4,5 pg/ml e 2,3 pg/ml, p< 0,05. Dentre essas pacientes (n=32, 65,5% apresentavam endometriose profunda. Pacientes com endometriose e infertilidade apresentavam concentrações maiores de IL-2 no fluido peritoneal quando comparadas com controle (média 5,9 pg/ml e 0,2 pg/ml, p< 0,05, sendo que neste grupo, 63,5% (n=14 apresentavam endometriose profunda. Foi observada também maior concentração de IL-10 nas pacientes que apresentavam endometriose ovariana quando comparadas às sem esse tipo de endometriose, assim como quando comparadas às pacientes do grupo controle (média 50pg/ml, 18,7pg/ml e 25,7pg/ml, p<0,05. CONCLUSÃO: Estes resultados sugerem que quando dados clínicos específicos associam-se a uma produção elevada de certas citocinas, ocorre um padrão de resposta Th1 que pode estar associado à endometriose profunda.

Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

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Jennifer M. Monk

2014-01-01

Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

Improved techniques for the analysis of experiments with polarized targets. [1 to 2 GeV/c, polarization

Energy Technology Data Exchange (ETDEWEB)

Barrelet, E.

1975-06-01

An experiment was performed at the Bevatron to measure the polarization in the reaction ..pi../sup -/p ..-->.. ..pi../sup 0/n from a polarized target, at beam momenta between 1 and 2 GeV/c. Concentration is placed on the original aspects of our analysis, in particular: the geometrical reconstruction of the elastic events; the use of the high analyzing power of the reaction studied to probe the polarization of the target in magnitude and distribution; a study of the statistical estimation of the polarization parameter; a detailed study of the quasielastic background. (JFP)

A Longitudinal Study of the Role of T Cell subset, Th1/Th2 cytokines ...

African Journals Online (AJOL)

A Longitudinal Study of the Role of T Cell subset, Th1/Th2 cytokines and antiplasmodial antibodies in uncomplicated Malaria in a Village Population Chronically Exposed to Plasmodium falciparum Malaria.

First polarization-engineered compressively strained AlInGaN barrier enhancement-mode MISHFET

International Nuclear Information System (INIS)

Hahn, Herwig; Reuters, Ben; Wille, Ada; Ketteniss, Nico; Kalisch, Holger; Vescan, Andrei; Benkhelifa, Fouad; Ambacher, Oliver

2012-01-01

One current focus of research is the realization of GaN-based enhancement-mode devices. A novel approach for the realization of enhancement-mode behaviour is the utilization of polarization matching between the barrier and the GaN buffer. Yet, the utilization of a quaternary barrier combining polarization engineering together with a large conduction band offset has not been demonstrated so far. Here, epitaxially grown, compressively strained AlInGaN is applied as a nearly polarization-matched barrier layer on GaN resulting in enhancement-mode operation. The insulated-gate devices are fabricated gate-first with Al 2 O 3 as gate dielectric. Passivated metal insulator semiconductor heterostructure field effect transistors yielded threshold voltages (V th ) of up to +1 V. The devices withstand negative and positive gate-biased stress and a positive V th is maintained even after long-time negative bias stress. (paper)

The molecular orientation of CO on Pd(1 1 1): a polarization-dependent SFG study

Science.gov (United States)

Galletto, Paolo; Unterhalt, Holger; Rupprechter, Günther

2003-01-01

The molecular orientation of carbon monoxide adsorbed on Pd(1 1 1) was examined by sum frequency generation (SFG) vibrational spectroscopy utilizing different polarization combinations of the visible and SFG light. This allows to determine the CO tilt angle with respect to the substrate, provided that a proper optical model for the interface can be defined. It is demonstrated that it is essential to invoke the βaac hyperpolarizability into the analysis and that polarization-dependent SFG of CO/Pd(1 1 1) yields information on βaac/ βccc rather than the tilt angle.

Opportunity's View After Drive on Sol 1806 (Vertical)

Science.gov (United States)

2009-01-01

NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 60.86 meters (200 feet) on the 1,806th Martian day, or sol, of Opportunity's surface mission (Feb. 21, 2009). North is at the center; south at both ends. Tracks from the drive extend northward across dark-toned sand ripples and light-toned patches of exposed bedrock in the Meridiani Planum region of Mars. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). Engineers designed the Sol 1806 drive to be driven backwards as a strategy to redistribute lubricant in the rovers wheels. The right-front wheel had been showing signs of increased friction. The rover's position after the Sol 1806 drive was about 2 kilometer (1.2 miles) south southwest of Victoria Crater. Cumulative odometry was 14.74 kilometers (9.16 miles) since landing in January 2004, including 2.96 kilometers (1.84 miles) since climbing out of Victoria Crater on the west side of the crater on Sol 1634 (August 28, 2008). This view is presented as a vertical projection with geometric seam correction.

Wind-Sculpted Vicinity After Opportunity's Sol 1797 Drive (Vertical)

Science.gov (United States)

2009-01-01

NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 111 meters (364 feet) on the 1,797th Martian day, or sol, of Opportunity's surface mission (Feb. 12, 2009). North is at the center; south at both ends. Tracks from the drive recede northward across dark-toned sand ripples in the Meridiani Planum region of Mars. Patches of lighter-toned bedrock are visible on the left and right sides of the image. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). This view is presented as a vertical projection with geometric seam correction.

The possibilities of using scale-selective polarization cartography in diagnostics of myocardium pathologies

Science.gov (United States)

Ushenko, Yu. A.; Wanchuliak, O. Y.

2013-06-01

The optical model of polycrystalline networks of myocardium protein fibrils is presented. The technique of determining the coordinate distribution of polarization azimuth of the points of laser images of myocardium histological sections is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order) parameters are presented which characterize distributions of wavelet-coefficients polarization maps of myocardium layers and death reasons.

New shapes of light-cone distributions of the transversely polarized ρ-mesons

International Nuclear Information System (INIS)

Bakulev, A.P.; Mikhajlov, S.V.

2000-01-01

The leading twist light-cone distributions for transversely polarized ρ-, ρ ' - and b 1 mesons are reanalyzed in the framework of QCD sum rules with nonlocal condensates. Using different kinds of sum rules to obtain reliable predictions, we estimate the 2-, 4-, 6- and 8-th moments for transversely polarized ρ- and ρ ' -meson distributions and reestimate tensor couplings f ρ,ρ ' ,b 1 T . It is stressed that the results of standard sum rules also support our estimation of the second moment of the transversely polarized ρ-meson distribution. New models for light-cone distributions are briefly discussed. Our results are compared with those found by Ball and Braun (1996), and the latter is shown to be incomplete

Polarization measurements of auroral kilometric radiation by Dynamics Explorer-1

International Nuclear Information System (INIS)

Shawhan, S.D.; Gurnett, D.A.

1982-01-01

The plasma wave instrument (PWI) on the Dynamics Explorer-1 has been used to measure polarization of auroral kilometric radiation (AKR) at frequencies of 50 to 400 kHz in both the northern and the southern nightside auroral regions at altitudes of 1 to 3 R/sub E/ above the AKR source regions. The AKR polarization sense is found to be the same as the right hand polarized auroral hiss found in the frequency range of 0.8 to 6.4 kHz. Consequently, these unambiguous direct polarization measurements of AKR lead to the conclusion that AKR escapes the magnetosphere in the R-X mode. Since DE-1 is close to the source region, it can be inferred that AKR is generated predominately in the R-X mode

Tracking polar lows in CLM

Energy Technology Data Exchange (ETDEWEB)

Zahn, M.; Storch, H. von [Inst. for Coastal Research, GKSS Research Center, Geesthacht (Germany); Meteorological Inst., Univ. of Hamburg (Germany)

2008-08-15

Polar lows are severe cyclones in sub-polar oceans sized beyond the resolved scale of existing global reanalysis products. We used the NCEP/NCAR reanalyses data to drive a regional climate model (CLM) in order to reproduce finer resolved atmospheric fields over the North Atlantic over a two year period. In these fields we detected polar lows by means of a detection algorithm based on a spatial digital bandpass filter. CLM was run in two different ways, the conventional way and with additionally prescribing the analysed large scale situation. The resulting temporal and spatial distributions of polar lows between the different simulations are compared. A reasonable seasonal cycle and spatial distribution was found for all simulations. A lower number of polar lows in the spectral nudged simulation indicates a closer vicinity to reality. Higher temporal and spatial variability between the conventional simulations suggest a more random generation of polar lows. Frequency distributions of track-lengths reveal shorter tracks when nudging is applied. Maximum wind speeds reveal only minor, insignificant differences between all runs and are higher in conventional mode. (orig.)

Curcumin attenuates the scurfy-induced immune disorder, a model of IPEX syndrome, with inhibiting Th1/Th2/Th17 responses in mice.

Science.gov (United States)

Lee, Gihyun; Chung, Hwan-Suck; Lee, Kyeseok; Lee, Hyeonhoon; Kim, Minhwan; Bae, Hyunsu

2017-09-15

Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects. The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period. C57BL/6 mice were separated into scurfy or wild-type litter mate groups by genotyping, and each group subsequently was separated into 2 subgroups that were fed a 1% curcumin containing or normal diet from the last day of breast-feeding. After weaning, pups were fed either a 1% curcumin containing or normal diet until all scurfy mice die for survival data. To elucidate immune cell proportions in spleen and lymph nodes, cells were analyzed by flowcytometry. Cellular cytokine production was accessed to investigate the effects of curcumin in T cell differentiation in vitro. Scurfy mice fed a 1% curcumin diet survived 4.0-fold longer compared to scurfy (92.5 days) mice fed a normal diet (23 days). A curcumin diet decreased all of the Th1/Th2/Th17 cell populations and attenuated diverse symptoms such as splenomegaly in scurfy mice. In vitro experiments showed that curcumin treatment directly decreased the Th1/Th2/Th17 cytokine production of IFN-γ, IL-4, and IL-17A in CD4 + T cells. Curcumin diet attenuated the scurfy-induced immune disorder, a model of IPEX syndrome, by inhibiting Th1/Th2/Th17 responses in mice. These results have implications for improving clinical therapy for patients with IPEX and other T cell related autoimmune diseases. Copyright © 2017 Elsevier GmbH. All rights reserved.

Convection flow structure in the central polar cap

Science.gov (United States)

Bristow, W. A.

2017-12-01

A previous study of spatially averaged flow velocity in the central polar cap [Bristow et al., 2015] observed under steady IMF conditions found that it was extremely rare for the average to exceed 850 m/s (less than 0.2 % of the time). Anecdotally, however it is not uncommon to observe line-of-sight velocities in excess of 100 m/s in the McMurdo radar field of view directly over the magnetic pole. This discrepancy motivated this study, which examines the conditions under which high-velocity flows are observed at latitudes greater than 80° magnetic latitude. It was found that highly structured flows are common in the central polar cap, which leads to the flow within regions to have significant deviation from the average. In addition, the high-speed flow regions are usually directed away from the earth-sun line. No specific set of driving conditions was identified to be associated with high-speed flows. The study did conclude that 1)Polar cap velocities are generally highly structured. 2)Flow patterns typically illustrate narrow channels, vortical flow regions, and propagating features. 3) Persistent waves are a regular occurrence. 3)Features are observed to propagate from day side to night side, and from night side to day side.. 4)Convection often exhibits significant difference between the two hemispheres. And 5)About 10% of the time the velocity somewhere in the cap exceeds 1 Km/s The presentation will conclude with a discussion of the physical reasons for the flow structure. Bristow, W. A., E. Amata, J. Spaleta, and M. F. Marcucci (2015), Observations of the relationship between ionospheric central polar cap and dayside throat convection velocities, and solar wind/IMF driving, J. Geophys. Res. Space Physics, 120, doi:10.1002/2015JA021199.

Opportunity's View After Long Drive on Sol 1770

Science.gov (United States)

2009-01-01

NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 104 meters (341 feet) on the 1,770th Martian day, or sol, of Opportunity's surface mission (January 15, 2009). Tracks from the drive extend northward across dark-toned sand ripples and light-toned patches of exposed bedrock in the Meridiani Planum region of Mars. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). Prior to the Sol 1770 drive, Opportunity had driven less than a meter since Sol 1713 (November 17, 2008), while it used the tools on its robotic arm first to examine a meteorite called 'Santorini' during weeks of restricted communication while the sun was nearly in line between Mars and Earth, then to examine bedrock and soil targets near Santorini. The rover's position after the Sol 1770 drive was about 1.1 kilometer (two-thirds of a mile) south southwest of Victoria Crater. Cumulative odometry was 13.72 kilometers (8.53 miles) since landing in January 2004, including 1.94 kilometers (1.21 miles) since climbing out of Victoria Crater on the west side of the crater on Sol 1634 (August 28, 2008). This view is presented as a cylindrical projection with geometric seam correction.

Changes in the Ratio of Tc1/Tc2 and Th1/Th2 Cells but Not in Subtypes of NK-Cells in Preeclampsia

Directory of Open Access Journals (Sweden)

Yayi Hou

2007-06-01

Full Text Available It has been suggested that natural killer (NK cell activity and Th1 immunitymay be involved in the pathogenesis of preeclampsia. This study aimed to investigate theimmunophenotypes of NK cells and type 1/type 2 immunity in both decidua and maternalperipheral blood between normal (n=11 and preeclamptic pregnant women (n=20 by flowcytometry. The results showed that no significant difference was observed between patientsand controls by detecting CD56+ CD69+ and CD56+ CD94+ NK cells in both peripheralblood and decidua. Moreover, in preeclamptic patients, decreased percentages of Tc2 andTh2 cells and the increased ratios of Tc1/Tc2 were determined in both decidua andmaternal peripheral blood. In addition, the ratio of Th1/Th2 in peripheral blood alsoincreased. There was no significant difference of immunophenotypes of uNK cells betweenpreeclampsia and normal pregnancy. Local decidua and systematic immunity did notcorrelate with each other. These results suggest that the type 1/type 2 immunity shifted totype 1 immunity including Th1 and Tc1 cells may contribute to the patho-genesis ofpreeclampsia.

P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria.

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Érika Machado de Salles

2017-08-01

Full Text Available A complete understanding of the mechanisms underlying the acquisition of protective immunity is crucial to improve vaccine strategies to eradicate malaria. However, it is still unclear whether recognition of damage signals influences the immune response to Plasmodium infection. Adenosine triphosphate (ATP accumulates in infected erythrocytes and is released into the extracellular milieu through ion channels in the erythrocyte membrane or upon erythrocyte rupture. The P2X7 receptor senses extracellular ATP and induces CD4 T cell activation and death. Here we show that P2X7 receptor promotes T helper 1 (Th1 cell differentiation to the detriment of follicular T helper (Tfh cells during blood-stage Plasmodium chabaudi malaria. The P2X7 receptor was activated in CD4 T cells following the rupture of infected erythrocytes and these cells became highly responsive to ATP during acute infection. Moreover, mice lacking the P2X7 receptor had increased susceptibility to infection, which correlated with impaired Th1 cell differentiation. Accordingly, IL-2 and IFNγ secretion, as well as T-bet expression, critically depended on P2X7 signaling in CD4 T cells. Additionally, P2X7 receptor controlled the splenic Tfh cell population in infected mice by promoting apoptotic-like cell death. Finally, the P2X7 receptor was required to generate a balanced Th1/Tfh cell population with an improved ability to transfer parasite protection to CD4-deficient mice. This study provides a new insight into malaria immunology by showing the importance of P2X7 receptor in controlling the fine-tuning between Th1 and Tfh cell differentiation during P. chabaudi infection and thus in disease outcome.

Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention.

Science.gov (United States)

Nocera, Nadia F; Lee, M Catherine; De La Cruz, Lucy M; Rosemblit, Cinthia; Czerniecki, Brian J

2016-01-01

The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy. Interestingly, response to HER-2 targeted therapies correlates with presence of immune response genes in the breast. Th1 cell production of the cytokines interferon gamma (IFNγ) and TNFα can enhance MHC class I expression, PD-L1 expression, augment apoptosis and tumor senescence, and enhances growth inhibition of many anti-breast cancer agents, including anti-estrogens and HER-2 targeted therapies. Recently, we have identified that a loss of anti-HER-2 CD4 Th1 in peripheral blood occurs during breast tumorigenesis and is dramatically diminished, even in Stage I breast cancers. The loss of anti-HER-2 Th1 response is specific and not readily reversed by standard therapies. In fact, this loss of anti-HER-2 Th1 response in peripheral blood correlates with lack of complete response to neoadjuvant therapy and diminished disease-free survival. This defect can be restored with HER-2 vaccinations in both DCIS and IBC. Correcting the anti-HER-2 Th1 response may have significant impact in improving response to HER-2 targeted therapies. Development of immune monitoring systems for anti-HER-2 Th1 to identify patients at risk for recurrence could be critical to improving outcomes, since the anti-HER-2 Th1 response can be restored by vaccination. Correction of the cellular immune response against HER-2 may prevent recurrence in high-risk patients with DCIS and IBC at risk of developing new or recurrent breast cancer.

Update of the Polar SWIFT model for polar stratospheric ozone loss (Polar SWIFT version 2)

Science.gov (United States)

Wohltmann, Ingo; Lehmann, Ralph; Rex, Markus

2017-07-01

The Polar SWIFT model is a fast scheme for calculating the chemistry of stratospheric ozone depletion in polar winter. It is intended for use in global climate models (GCMs) and Earth system models (ESMs) to enable the simulation of mutual interactions between the ozone layer and climate. To date, climate models often use prescribed ozone fields, since a full stratospheric chemistry scheme is computationally very expensive. Polar SWIFT is based on a set of coupled differential equations, which simulate the polar vortex-averaged mixing ratios of the key species involved in polar ozone depletion on a given vertical level. These species are O3, chemically active chlorine (ClOx), HCl, ClONO2 and HNO3. The only external input parameters that drive the model are the fraction of the polar vortex in sunlight and the fraction of the polar vortex below the temperatures necessary for the formation of polar stratospheric clouds. Here, we present an update of the Polar SWIFT model introducing several improvements over the original model formulation. In particular, the model is now trained on vortex-averaged reaction rates of the ATLAS Chemistry and Transport Model, which enables a detailed look at individual processes and an independent validation of the different parameterizations contained in the differential equations. The training of the original Polar SWIFT model was based on fitting complete model runs to satellite observations and did not allow for this. A revised formulation of the system of differential equations is developed, which closely fits vortex-averaged reaction rates from ATLAS that represent the main chemical processes influencing ozone. In addition, a parameterization for the HNO3 change by denitrification is included. The rates of change of the concentrations of the chemical species of the Polar SWIFT model are purely chemical rates of change in the new version, whereas in the original Polar SWIFT model, they included a transport effect caused by the

Adjustable speed drive study, part 1

Science.gov (United States)

Wallace, A.

1989-08-01

Advances in speed control for motors in recent years, notably those in power electronics, have widened the range of application for several adjustable speed drive (ASD) types to include the smaller horsepower sizes. The dc motor drive, formerly in almost universal use for speed control, is being challenged by the high efficiency induction motor/pulse width modulation (PWM) drive; and for special small horsepower size applications, by the permanent magnet motor/PWM inverter drive or by the switched reluctance motor drive. The main characteristics of the several ASD types suitable for small horsepower size applications are discussed, as well as their unwanted side effects: poor power factor, harmonic distortion of the supply, acoustic noise, and electromagnetic interference. A procedure is recommended for determining which, if any, ASD to use.

Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells.

Science.gov (United States)

Haabeth, Ole Audun Werner; Lorvik, Kristina Berg; Yagita, Hideo; Bogen, Bjarne; Corthay, Alexandre

The role of inflammation in cancer is controversial as both tumor-promoting and tumor-suppressive aspects of inflammation have been reported. In particular, it has been shown that pro-inflammatory cytokines, like interleukin-1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor α (TNFα), may either promote or suppress cancer. However, the cellular and molecular basis underlying these opposing outcomes remains enigmatic. Using mouse models for myeloma and lymphoma, we have recently reported that inflammation driven by tumor-specific T helper 1 (Th1) cells conferred protection against B-cell cancer and that interferon-γ (IFN-γ) was essential for this process. Here, we have investigated the contribution of several inflammatory mediators. Myeloma eradication by Th1 cells was not affected by inhibition of TNF-α, TNF-related weak inducer of apoptosis (TWEAK), or TNF-related apoptosis-inducing ligand (TRAIL). In contrast, cancer elimination by tumor-specific Th1 cells was severely impaired by the in vivo neutralization of both IL-1α and IL-1β (collectively named IL-1) with IL-1 receptor antagonist (IL-1Ra). The antitumor functions of tumor-specific Th1 cells and tumor-infiltrating macrophages were both affected by IL-1 neutralization. Secretion of the Th1-derived cytokines IL-2 and IFN-γ at the incipient tumor site was severely reduced by IL-1 blockade. Moreover, IL-1 was shown to synergize with IFN-γ for induction of tumoricidal activity in tumor-infiltrating macrophages. This synergy between IL-1 and IFN-γ may explain how inflammation, when driven by tumor-specific Th1 cells, represses rather than promotes cancer. Collectively, the data reveal a central role of inflammation, and more specifically of the canonical pro-inflammatory cytokine IL-1, in enhancing Th1-mediated immunity against cancer.

Influence of Zr substitution on the stabilization of ThMn12-type (Nd1−αZrα(Fe0.75Co0.2511.25Ti0.75N1.2−1.4 (α = 0–0.3 compounds

Directory of Open Access Journals (Sweden)

N. Sakuma

2016-05-01

Full Text Available The influence of Zr substitution in ThMn12 compounds was investigated using strip casting alloys. It was found that Zr substitution stabilized (Nd1−αZrα(Fe0.75Co0.2511.25Ti0.75N1.2−1.4 (α = 0–0.3 compounds. Specifically, a reduction in the lattice constant along the a-axis was observed. Energy-dispersive X-ray spectroscopy mapping combined with Cs-corrected scanning transmission electron microscopy indicated that Zr atoms preferentially occupied Nd 2a sites. Both the magnetic anisotropy field and saturation polarization were maximum at Zr substitution ratio α = 0.1. The (Nd1−αZrα(Fe0.75Co0.2511.25Ti0.75N1.2−1.4 (α = 0–0.3 compounds displayed higher saturation polarization than Nd2Fe14B at high temperatures.

Polarization-dependent force driving the Eg mode in bismuth under optical excitation: comparison of first-principles theory with ultra-fast x-ray experiments

Science.gov (United States)

Fahy, Stephen; Murray, Eamonn

2015-03-01

Using first principles electronic structure methods, we calculate the induced force on the Eg (zone centre transverse optical) phonon mode in bismuth immediately after absorption of a ultrafast pulse of polarized light. To compare the results with recent ultra-fast, time-resolved x-ray diffraction experiments, we include the decay of the force due to carrier scattering, as measured in optical Raman scattering experiments, and simulate the optical absorption process, depth-dependent atomic driving forces, and x-ray diffraction in the experimental geometry. We find excellent agreement between the theoretical predictions and the observed oscillations of the x-ray diffraction signal, indicating that first-principles theory of optical absorption is well suited to the calculation of initial atomic driving forces in photo-excited materials following ultrafast excitation. This work is supported by Science Foundation Ireland (Grant No. 12/IA/1601) and EU Commission under the Marie Curie Incoming International Fellowships (Grant No. PIIF-GA-2012-329695).

Correlation Between Th1, Th2 Cells and Levels of Serum MMP-2, MMP-9 in Children with Asthma

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Xuan WANG

2015-12-01

Full Text Available Abstract Objective: To explore the correlation between Th1 and Th2 cells and the levels of serum matrix metalloproteinase-2 (MMP-2 and MMP-9 in children with asthma. Methods: A total of 89 children with asthma were divided into acute group (n=48 and chronic group (n=41 according to the course of disease, and 40 healthy children at the same term were collected as control group. The ratios of Th1 and Th2 cells as well as levels of MMP-2 and MMP-9 were compared in three groups, and the correlation between Th1 and Th2 cells and levels of MMP-2, MMP-9 was analyzed in acute group and chronic group. Results: When compared with control group, the ratios of Th1 and Th2 cells went down in both acute group and chronic group (P<0.01, while the levels of serum MMP-2 and MMP-9 up (P<0.01. The levels of serum MMP-2 and MMP-9 in acute group were dramatically higher than those in chronic group, and there was statistical significance (P<0.01. Pearson correlation analysis revealed that there was no significant correlation between Th1 and Th2 cells and MMP-2 level (r=0.148, P=0.314, r=0.299, P=0.058; r=0.183, P=0.214, r=0.289, P=0.067, whereas both Th1 and Th2 cells were negatively correlated with MMP-9 level in acute group and chronic group (r=-0.489, P=0.000, r=-0.324, P=0.039; r=-0.352, P=0.014, r=-0.357, P=0.022. Conclusion: Aberrant secretion of Th cells can not only damage the immune function of children with asthma, but also decrease the level of serum MMP-9, consequently affecting the collagen degradation and airway remodeling.

Can GRACE Explain Some of the Main Interannual Polar Motion Signatures?

Science.gov (United States)

Adhikari, S.; Ivins, E. R.; Larour, E. Y.

2016-12-01

GRACE has provided a series of monthly solutions for water mass transport that now span a 14-year period. A natural question to ask is how much of this mass transport information might be used to reconstruct, theoretically, the non-tidal and non-Chandlerian polar motion at interannual time scales. Reconstruction of the pole position at interannual time scales since 2002 has been performed by Chen et al. (2013, GRL) and Adhikari and Ivins (2016, Science Advances). (The main feature of polar motion that has been evolving since the mid 1990's is the increasing dominance of Greenland ice mass loss.) Here we discuss this reconstruction and the level of error that occurs because of missing information about the spherical harmonic degree 1 and 2 terms and the lack of terms associated with angular momentum transfer in the Louiville equations. Using GRACE observations and complementary solutions of self-attraction/loading problem on an elastically compressible rotating earth, we show that ice mass losses from polar ice sheets, and when combined with changes in continental hydrology, explain nearly the entire amplitude (83±23%) and mean directional shift (within 5.9±7.6°) of recently observed eastward polar motion. We also show that decadal scale pole variations are directly linked to global changes in continental hydrology. The energy sources for such motions are likely to be associated with decadal scale ocean and atmospheric oscillations that also drive 20th century continental wet-dry variability. Interannual variability in pole position, therefore, offers a tool for assessing past stability of our climate, and for the future, now faced with an increased intensity in the water cycle and more vulnerable to ice sheet instability. Figure caption: Observed and reconstructed mean annual pole positions with respect to the 2003-2015 mean position. Blue error band is associated with the reconstructed solution; red signifies additional errors that are related to uncertainty in

Non-polarized cytokine profile of a long-term non-progressor HIV infected patient.

Science.gov (United States)

Pina, Ana Flávia; Matos, Vanessa Terezinha Gubert de; Bonin, Camila Mareti; Dal Fabbro, Márcia Maria Ferrairo Janini; Tozetti, Inês Aparecida

The HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without antiretroviral therapy. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast IL-4 was identified. Host-related factors could help explain such a level of infection control, namely the differentiated modulation of the cellular immune response and a non-polarized cytokine response of the TH1 and TH2 profiles. Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Alleviation of collagen-induced arthritis by the benzoxathiole derivative BOT-4-one in mice: Implication of the Th1- and Th17-cell-mediated immune responses.

Science.gov (United States)

Kim, Byung-Hak; Yoon, Bo Ruem; Kim, Eun Kyoung; Noh, Kum Hee; Kwon, Sun-Ho; Yi, Eun Hee; Lee, Hyun Gyu; Choi, Jung Sook; Kang, Seong Wook; Park, In-Chul; Lee, Won-Woo; Ye, Sang-Kyu

2016-06-15

Autoimmune rheumatoid arthritis is characterized by chronic inflammation and hyperplasia in the synovial joints. Although the cause of rheumatoid arthritis is largely unknown, substantial evidence has supported the importance of immune cells and inflammatory cytokines in the initiation and progression of this disease. Herein, we demonstrated that the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) alleviated type II collagen-induced arthritis in a mouse model. The levels of pro-inflammatory cytokines are elevated in both human patients with rheumatoid arthritis and mice with collagen-induced arthritis. BOT-4-one treatment reduced the levels of pro-inflammatory cytokines in mice and endotoxin-stimulated macrophages. BOT-4-one treatment suppressed the polarization of Th1- and Th17-cell subsets by inhibiting the expression and production of their lineage-specific master transcription factors and cytokines, as well as activation of signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited mitogen-activated protein kinase and NF-kappaB signaling as well as the transcriptional activities and DNA-binding of transcription factors, including activator protein-1, cAMP response element-binding protein and NF-kappaB. Our results suggest that BOT-4-one may have therapeutic potential for the treatment of chronic inflammation associated with autoimmune rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Mode of dendritic cell activation: the decisive hand in Th2/Th17 cell differentiation. Implications in asthma severity?

Science.gov (United States)

Vroman, Heleen; van den Blink, Bernt; Kool, Mirjam

2015-02-01

Asthma is a heterogeneous chronic inflammatory disease of the airways, with reversible airflow limitations and airway remodeling. The classification of asthma phenotypes was initially based on different combinations of clinical symptoms, but they are now unfolding to link biology to phenotype. As such, patients can suffer from a predominant eosinophilic, neutrophilic or even mixed eosinophilic/neutrophilic inflammatory response. In adult asthma patients, eosinophilic inflammation is usually seen in mild-to-moderate disease and neutrophilic inflammation in more severe disease. The underlying T cell response is predominated by T helper (Th) 2, Th17, or a mixed Th2/Th17 cell immune response. Dendritic cells (DCs) are "professional" antigen presenting cells (APCs), since their principal function is to present antigens and induce a primary immune response in resting naive T cells. DCs also drive the differentiation into distinctive Th subsets. The expression of co-stimulatory molecules and cytokines by DCs and surrounding cells determines the outcome of Th cell differentiation. The nature of DC activation will determine the expression of specific co-stimulatory molecules and cytokines, specifically needed for induction of the different Th cell programs. Thus DC activation is crucial for the subsequent effector Th immune responses. In this review, we will discuss underlying mechanisms that initiate DC activation in favor of Th2 differentiation versus Th1/Th17 and Th17 differentiation in the development of mild versus moderate to severe asthma. Copyright © 2014 Elsevier GmbH. All rights reserved.

Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation.

Science.gov (United States)

Sido, Jessica M; Jackson, Austin R; Nagarkatti, Prakash S; Nagarkatti, Mitzi

2016-09-01

∆(9)-Tetrahydrocannabinol (THC) is one of the major bioactive cannabinoids derived from the Cannabis sativa plant and is known for its anti-inflammatory properties. Delayed-type hypersensitivity (DTH) is driven by proinflammatory T helper cells including the classic inflammatory Th1 lineage as well as the more recently discovered Th17 lineage. In the current study, we investigated whether THC can alter the induction of Th1/Th17 cells involved in mBSA-induced DTH response. THC treatment (20 mg/kg) of C57BL/6 mice with DTH caused decreased swelling and infiltration of immune cells at the site of antigen rechallenge. Additionally, THC treatment decreased lymphocyte activation as well as Th1/Th17 lineage commitment, including reduced lineage-specific transcription factors and cytokines. Interestingly, while DTH caused an overexpression of miR-21, which increases Th17 differentiation via SMAD7 inhibition, and downregulation of miR-29b, an IFN-γ inhibitor, THC treatment reversed this microRNA (miR) dysregulation. Furthermore, when we transfected primary cells from DTH mice with miR-21 inhibitor or miR-29b mimic, as seen with THC treatment, the expression of target gene message was directly impacted increasing SMAD7 and decreasing IFN-γ expression, respectively. In summary, the current study suggests that THC treatment during DTH response can simultaneously inhibit Th1/Th17 activation via regulation of microRNA (miRNA) expression. • THC treatment inhibits simultaneous Th1/Th17 driven inflammation. • THC treatment corrects DTH-mediated microRNA dysregulation. • THC treatment regulates proinflammatory cytokines and transcription factors.

Evidence for mouse Th1- and Th2-like helper T cells in vivo. Selective reduction of Th1-like cells after total lymphoid irradiation

International Nuclear Information System (INIS)

Bass, H.; Mosmann, T.; Strober, S.

1989-01-01

Purified CD4+ BALB/c spleen T cells obtained 4-6 wk after total lymphoid irradiation (TLI) helped normal syngeneic B cells to produce a vigorous antibody response to TNP keyhole limpet hemocyanin in adoptive cell transfer experiments. However, the same cells failed to transfer delayed-type hypersensitivity to the adoptive hosts as measured by a foot pad swelling assay. In addition, purified CD4+ cells from TLI-treated mice were unable to induce graft vs. host disease in lethally irradiated allogeneic C57BL/Ka recipient mice. In response to mitogen stimulation, unfractionated spleen cells obtained from TLI mice secreted normal levels of IL-4 and IL-5, but markedly reduced levels of IL-2 and INF-gamma. A total of 229 CD4+ clones from spleen cells of both normal and TLI-treated mice were established, and the cytokine secretion pattern from each clone was analyzed. The results demonstrate that the ratio of Th1- and Th2-like clones in the spleens of normal BALB/c mice is 1:0.6, whereas the ratio in TLI mice is approximately 1:7. These results suggest that Th2-like cells recover rapidly (at approximately 4-6 wk) after TLI treatment and account for the early return of antibody helper activity and secretion of IL-4 and IL-5, but Th1-like cells recover more slowly (in approximately 3 mo) after irradiation, and this accounts for the deficit in cell-mediated immunity and the reduced amount of IL-2 and IFN-gamma secretion

C5a regulates IL-12+ DC migration to induce pathogenic Th1 and Th17 cells in sepsis.

Directory of Open Access Journals (Sweden)

Ning Ma

Full Text Available OBJECTIVE: It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs to stimulate adaptive immune cells such as Th1 and Th17 in sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP. CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+DC, IFNγ(+Th1, and IL-17(+Th17 cells were analyzed by flow cytometry. IL-12 was measured by ELISA. RESULTS: Our studies here showed that C5a induced IL-12(+DC cell migration from the peritoneal cavity to peripheral blood and lymph nodes. Furthermore, IL-12(+DC cells induced the expansion of pathogenic IFNγ(+Th1 and IL-17(+Th17 cells in peripheral blood and lymph nodes. Moreover, IL-12, secreted by DC cells in the peritoneal cavity, is an important factor that prevents the development of sepsis. CONCLUSION: Our data suggests that C5a regulates IL-12(+DC cell migration to induce pathogenic Th1 and Th17 cells in sepsis.

Spirit Begins Drive Around Home Plate

Science.gov (United States)

2009-01-01

The hazard avoidance camera on the front of NASA's Mars Exploration Rover Spirit took this image after a drive by Spirit on the 1,829th Martian day, or sol, of Spirit's mission on the surface of Mars (Feb. 24, 2009). On Sol 1829, Spirit drove 6.29 meters (21 feet) northwestward, away from the northern edge of the low plateau called 'Home Plate.' The track dug by the dragged right-front wheel as the rover drove backward is visible in this image, receding toward the southeast. Rock layers of the northern slope of Home Plate are visible in the upper right portion of the image. In sols prior to 1829, the rover team had been trying to maneuver Spirit to climb onto the northern edge of Home Plate, ready to drive southward across the top of the plateau toward science destinations south of Home Plate. The Sol 1829 drive was the first move of a revised strategy to circle at least partway around Home Plate on the trek toward the sites south of the plateau.

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice.

Science.gov (United States)

Soria, I; López-Relaño, J; Viñuela, M; Tudela, J-I; Angelina, A; Benito-Villalvilla, C; Díez-Rivero, C M; Cases, B; Manzano, A I; Fernández-Caldas, E; Casanovas, M; Palomares, O; Subiza, J L

2018-04-01

Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM-allergoids administered sublingually in comparison with native allergens. Three immunization protocols (4-8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells. A quick antibody response and higher IgG2a/IgE ratio were observed with PM-allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL-4 ratio with a quick IL-10 production by submandibular LN cells. An increase in CD4 + CD25 high FOXP3 + Treg cells was detected in LNs and spleen of mice treated with PM-allergoids. These allergoids were better captured than native allergens by antigen-presenting (CD45 + MHC-II + ) cells obtained from the sublingual mucosa, including DCs (CD11b + ) and macrophages (CD64 + ). Importantly, all the differential effects induced by PM-allergoids were abolished when using oxidized instead of nonoxidized PM-allergoids. Our results demonstrate for the first time that PM-allergoids administered through the sublingual route promote the generation of Th1 and FOXP3 + Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen-presenting cells. © 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.

Therapeutic effect of dioscin on collagen-induced arthritis through reduction of Th1/Th2.

Science.gov (United States)

Guo, Yachun; Xing, Enhong; Song, Hongru; Feng, Guiying; Liang, Xiujun; An, Gao; Zhao, Xiaofei; Wang, Mi

2016-10-01

The aim of this study was to detect the therapeutic effect of dioscin on collagen-induced arthritis (CIA). Mice model of CIA was induced by chicken collagen II and arthritis index was assessed. After suspension of dioscin (100mg/kg/d) or triptolide was intragastrically administered, the left paw swelling and body weight of each mouse were measured. Then tissue samples were assayed by histopathological analysis. The levels of Th1 and Th2 were detected by flow cytometry. The expression of p-STAT1, p-STAT4 and p-STAT6 was demonstrated by western blot analysis, and T-bet and GATA-3 expression was detected by RT-PCR. The paw swelling and arthritis index were decreased and body weight was increased in the high dose of dioscin group compared to the model group (PTh1/Th2 in the dioscin group (0.82±0.24) and triptolide group (0.99±0.44) was lower than that in the model group (1.84±0.70, PTh1/Th2 cells, which could reduce the expression of p-STAT4, increase the expression of p-STAT6 and GATA3 in the synovial tissue. Copyright © 2016 Elsevier B.V. All rights reserved.

Measurement of the Polarized Structure Function $g_1^p$ at HERA

CERN Document Server

Ball, R.D.; Forte, S.; Hughes, V.W.; Lichtenstadt, J.; Ridolfi, G.; Ball, Richard D.; Deshpande, Abhay; Forte, Stefano; Hughes, Vernon W.; Lichtenstadt, Jechiel; Ridolfi, Giovanni

1996-01-01

We present estimates of possible data on spin-dependent asymmetries in inclusive scattering of high energy polarized electrons by high energy polarized protons at HERA, including statistical errors, and discuss systematic uncertainties. We show that these data would shed light on the small x behaviour of the polarized structure function g_1, and would reduce substantially the uncertainty on the determination of the polarized gluon distribution.

Update of the Polar SWIFT model for polar stratospheric ozone loss (Polar SWIFT version 2

Directory of Open Access Journals (Sweden)

I. Wohltmann

2017-07-01

Full Text Available The Polar SWIFT model is a fast scheme for calculating the chemistry of stratospheric ozone depletion in polar winter. It is intended for use in global climate models (GCMs and Earth system models (ESMs to enable the simulation of mutual interactions between the ozone layer and climate. To date, climate models often use prescribed ozone fields, since a full stratospheric chemistry scheme is computationally very expensive. Polar SWIFT is based on a set of coupled differential equations, which simulate the polar vortex-averaged mixing ratios of the key species involved in polar ozone depletion on a given vertical level. These species are O3, chemically active chlorine (ClOx, HCl, ClONO2 and HNO3. The only external input parameters that drive the model are the fraction of the polar vortex in sunlight and the fraction of the polar vortex below the temperatures necessary for the formation of polar stratospheric clouds. Here, we present an update of the Polar SWIFT model introducing several improvements over the original model formulation. In particular, the model is now trained on vortex-averaged reaction rates of the ATLAS Chemistry and Transport Model, which enables a detailed look at individual processes and an independent validation of the different parameterizations contained in the differential equations. The training of the original Polar SWIFT model was based on fitting complete model runs to satellite observations and did not allow for this. A revised formulation of the system of differential equations is developed, which closely fits vortex-averaged reaction rates from ATLAS that represent the main chemical processes influencing ozone. In addition, a parameterization for the HNO3 change by denitrification is included. The rates of change of the concentrations of the chemical species of the Polar SWIFT model are purely chemical rates of change in the new version, whereas in the original Polar SWIFT model, they included a transport effect

The diagnostic value of Th1/Th2 cell cytokine and thyroid autoantibody on autoimmune thyroid diseases

International Nuclear Information System (INIS)

Feng Xuemin; Qin Mingxiu; Zhao Yan

2008-01-01

To study the diagnostic value of Th1/Th2 cell cytokine and thyroid autoantibody in autoimmune thyroid diseases (AITD), 28 patients with Graves' disease (GD), 15 patients with hyperthyroidism and thyroiditis (GDIII), 13 patients with Hashimoto's hyperthyroidism (HTL), 21 patients with Hashimoto's thyroiditis(HT)and 20 healthy subjects were enrolled in this study. The serum concentrations of Th1 cytokine (IFN-γ) and Th2 cytokine (IL-4) were determined by ELISA. The serum levels of thyrotropin receptor antibodies (TRAb), thyroglobulin antibodies (TGAb) and thyroid peroxidase antibodies (TPOAb) were measured by RIA. The relationship between the serum levels of IFN-γ, IL-4 and TRAb, TGAb and TPOAb were analyzed. The results showed that IFN-γ levels from higher to lower in different groups were in the order of HT, HTL, GDIII, GD and the IL-4 were GD, GDIII, HTL, HT, respectively. There was significant difference in the IFN-γ (P<0.05) and IL-4 levels (P<0.01) between GDIII and HTL groups. There was no significant difference in TGAb and TPOAb between GDIII and HTL groups. In HT group, IFN-γ levels was positively correlated with TGAb and TPOAb (r=0.67,0.54,P<0.01). In GD group, IL-4 was positively correlated with TRAb (r =0.71,P<0.01). The imbalance of Th1/Th2 cell cytokine reflects pathologic change and abnormality of immune function in AITD patients. The detection of Th1/Th2 cell cytokine combined with thyroid autoantibody may be regarded as an indicator in the diagnosis of autoimmune thyroid diseases. (authors)

[Innovation drive is the original motive force of discipline construction: the developing road of Department of Burns and Plastic Surgery in the 309th Hospital of PLA].

Science.gov (United States)

Jia, C Y

2018-03-20

Discipline construction is a systematic project, covering clinic, teaching, scientific research, management, and humanity. Based on the perspective of innovation drive, from the aspects of discipline structure setting, specialized laboratory construction, sub-specialty formation, clinical characteristic and advantage formation, and management concept update, this article summarizes the growth process of Department of Burns and Plastic Surgery in the 309th Hospital of PLA.

Stable T-bet+GATA-3+ Th1/Th2 Hybrid Cells Arise In Vivo, Can Develop Directly from Naive Precursors, and Limit Immunopathologic Inflammation

Science.gov (United States)

Peine, Michael; Fröhlich, Anja; Hegazy, Ahmed N.; Kühl, Anja A.; Grevelding, Christoph G.; Höfer, Thomas; Hartmann, Susanne; Löhning, Max

2013-01-01

Differentiated T helper (Th) cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against parasites generate bifunctional Th1 and Th2 hybrid cells that co-express the lineage-specifying transcription factors T-bet and GATA-3 and co-produce Th1 and Th2 cytokines. The integration of Th1-promoting interferon (IFN)-γ and interleukin (IL)-12 signals together with Th2-favoring IL-4 signals commits naive Th cells directly and homogeneously to the hybrid Th1/2 phenotype. Specifically, IFN-γ signals are essential for T-bet+GATA-3+ cells to develop in vitro and in vivo by breaking the dominance of IL-4 over IL-12 signals. The hybrid Th1/2 phenotype is stably maintained in memory cells in vivo for months. It resists reprogramming into classic Th1 or Th2 cells by Th1- or Th2-promoting stimuli, which rather induce quantitative modulations of the combined Th1 and Th2 programs without abolishing either. The hybrid phenotype is associated with intermediate manifestations of both Th1 and Th2 cell properties. Consistently, hybrid Th1/2 cells support inflammatory type-1 and type-2 immune responses but cause less immunopathology than Th1 and Th2 cells, respectively. Thus, we propose the self-limitation of effector T cells based on the stable cell-intrinsic balance of two opposing differentiation programs as a novel concept of how the immune system can prevent excessive inflammation. PMID:23976880

Stable T-bet(+GATA-3(+ Th1/Th2 hybrid cells arise in vivo, can develop directly from naive precursors, and limit immunopathologic inflammation.

Directory of Open Access Journals (Sweden)

Michael Peine

Full Text Available Differentiated T helper (Th cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against parasites generate bifunctional Th1 and Th2 hybrid cells that co-express the lineage-specifying transcription factors T-bet and GATA-3 and co-produce Th1 and Th2 cytokines. The integration of Th1-promoting interferon (IFN-γ and interleukin (IL-12 signals together with Th2-favoring IL-4 signals commits naive Th cells directly and homogeneously to the hybrid Th1/2 phenotype. Specifically, IFN-γ signals are essential for T-bet(+GATA-3(+ cells to develop in vitro and in vivo by breaking the dominance of IL-4 over IL-12 signals. The hybrid Th1/2 phenotype is stably maintained in memory cells in vivo for months. It resists reprogramming into classic Th1 or Th2 cells by Th1- or Th2-promoting stimuli, which rather induce quantitative modulations of the combined Th1 and Th2 programs without abolishing either. The hybrid phenotype is associated with intermediate manifestations of both Th1 and Th2 cell properties. Consistently, hybrid Th1/2 cells support inflammatory type-1 and type-2 immune responses but cause less immunopathology than Th1 and Th2 cells, respectively. Thus, we propose the self-limitation of effector T cells based on the stable cell-intrinsic balance of two opposing differentiation programs as a novel concept of how the immune system can prevent excessive inflammation.

Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders

Directory of Open Access Journals (Sweden)

Hans O. Kalkman

2017-12-01

Full Text Available Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD. Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4 and IL13, which stimulate microglia and macrophages to adopt a phenotype referred to as ‘alternative activation’ or ‘M2A’. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor (BDNF and insulin-like growth factor-1. In ASD there is evidence for increased type-2 cytokines, microglia activation, M2A polarization, and increased levels of growth factors. In neurons, these growth factors drive a signal transduction pathway that leads to activation of the enzyme mammalian Target of Rapamycin (mTOR, and thereby to the inhibition of autophagy. Activation of mTOR is an effect that is also common to several of the genetic forms of autism. In the central nervous system, redundant synapses are removed via an autophagic process. Activation of mTOR would diminish the pruning of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases like food allergy, eczema or asthma would represent risk factors for autism spectrum disorders.

Dopamine Receptor D3 Signaling on CD4+ T Cells Favors Th1- and Th17-Mediated Immunity.

Science.gov (United States)

Contreras, Francisco; Prado, Carolina; González, Hugo; Franz, Dafne; Osorio-Barrios, Francisco; Osorio, Fabiola; Ugalde, Valentina; Lopez, Ernesto; Elgueta, Daniela; Figueroa, Alicia; Lladser, Alvaro; Pacheco, Rodrigo

2016-05-15

Dopamine receptor D3 (DRD3) expressed on CD4(+) T cells is required to promote neuroinflammation in a murine model of Parkinson's disease. However, how DRD3 signaling affects T cell-mediated immunity remains unknown. In this study, we report that TCR stimulation on mouse CD4(+) T cells induces DRD3 expression, regardless of the lineage specification. Importantly, functional analyses performed in vivo using adoptive transfer of OVA-specific OT-II cells into wild-type recipients show that DRD3 deficiency in CD4(+) T cells results in attenuated differentiation of naive CD4(+) T cells toward the Th1 phenotype, exacerbated generation of Th2 cells, and unaltered Th17 differentiation. The reciprocal regulatory effect of DRD3 signaling in CD4(+) T cells favoring Th1 generation and impairing the acquisition of Th2 phenotype was also reproduced using in vitro approaches. Mechanistic analysis indicates that DRD3 signaling evokes suppressor of cytokine signaling 5 expression, a negative regulator of Th2 development, which indirectly favors acquisition of Th1 phenotype. Accordingly, DRD3 deficiency results in exacerbated eosinophil infiltration into the airways of mice undergoing house dust mite-induced allergic response. Interestingly, our results show that, upon chronic inflammatory colitis induced by transfer of naive CD4(+) T cells into lymphopenic recipients, DRD3 deficiency not only affects Th1 response, but also the frequency of Th17 cells, suggesting that DRD3 signaling also contributes to Th17 expansion under chronic inflammatory conditions. In conclusion, our findings indicate that DRD3-mediated signaling in CD4(+) T cells plays a crucial role in the balance of effector lineages, favoring the inflammatory potential of CD4(+) T cells. Copyright © 2016 by The American Association of Immunologists, Inc.

Dynamical nuclear polarization using multi-colour control of color centers in diamond

Energy Technology Data Exchange (ETDEWEB)

Yang, Pengcheng [Huazhong University of Science and Technology, School of Physics, Wuhan (China); Huazhong University of Science and Technology, Center for Quantum Optical Science, Wuhan (China); Plenio, Martin B. [Universitaet Ulm, Institut fuer Theoretische Physik, Ulm (Germany); Universitaet Ulm, Center for Integrated Quantum Science and Technology, Ulm (Germany); Cai, Jianming [Huazhong University of Science and Technology, School of Physics, Wuhan (China); Huazhong University of Science and Technology, Center for Quantum Optical Science, Wuhan (China); Universitaet Ulm, Institut fuer Theoretische Physik, Ulm (Germany); Universitaet Ulm, Center for Integrated Quantum Science and Technology, Ulm (Germany)

2016-12-15

Dynamical nuclear polarization (DNP) transfers the polarization of electron spins at cryogenic temperatures to achieve strong nuclear polarization for applications in nuclear magnetic resonance. Recently introduced approaches employ optical pumping of nitrogen-vacancy (NV) centers in diamond to achieve DNP even at ambient temperatures. In such schemes microwave radiation is used to establish a Hartmann-Hahn condition between the NV electron spin and proximal nuclear spins to facilitate polarization transfer. For a single monochromatic microwave driving field, the Hartmann-Hahn condition cannot be satisfied for an ensemble of NV centers due to inhomogeneous broadening and reduces significantly the overall efficiency of dynamical nuclear polarization using an ensemble of NV centers. Here, we adopt generalized Hartmann-Hahn type dynamical nuclear polarization schemes by applying microwave driving fields with (multiple) time-modulated frequencies. We show that it is possible to enhance the effective coupling between an ensemble of NV center spins with inhomogeneous broadening and nuclear spins, thereby improving significantly the overall efficiency of dynamical nuclear polarization. This approach can also be used to achieve dynamical nuclear polarization of an ensemble of nuclei with a distribution of Larmor frequencies, which would be helpful in magnetic resonance spectroscopy using a single NV spin sensor. (orig.)

Moessbauer polarimetry using fluosilicates. Double motion drive and effective thickness measurements

Energy Technology Data Exchange (ETDEWEB)

Henry, M; Varret, F [Centre Universitaire du Mans, 72 (France)

1977-12-16

Calculations are made and spectra are obtained on linear experiments using single crystals. The energy coincidence between the source and the polarizer is achieved by using a double motion drive which moves the source at a constant velocity. Such an experiment provides an accurate determination of both the polarizer and the analyzer effective thicknesses.

Opportunity's View After Long Drive on Sol 1770 (Vertical)

Science.gov (United States)

2009-01-01

NASA's Mars Exploration Rover Opportunity used its navigation camera to take the images combined into this full-circle view of the rover's surroundings just after driving 104 meters (341 feet) on the 1,770th Martian day, or sol, of Opportunity's surface mission (January 15, 2009). This view is presented as a vertical projection with geometric seam correction. North is at the top. Tracks from the drive extend northward across dark-toned sand ripples and light-toned patches of exposed bedrock in the Meridiani Planum region of Mars. For scale, the distance between the parallel wheel tracks is about 1 meter (about 40 inches). Prior to the Sol 1770 drive, Opportunity had driven less than a meter since Sol 1713 (November 17, 2008), while it used the tools on its robotic arm first to examine a meteorite called 'Santorini' during weeks of restricted communication while the sun was nearly in line between Mars and Earth, then to examine bedrock and soil targets near Santorini. The rover's position after the Sol 1770 drive was about 1.1 kilometer (two-thirds of a mile) south southwest of Victoria Crater. Cumulative odometry was 13.72 kilometers (8.53 miles) since landing in January 2004, including 1.94 kilometers (1.21 miles) since climbing out of Victoria Crater on the west side of the crater on Sol 1634 (August 28, 2008).

High-temperature vaporization of thorium-uranium mixed monocarbide (Th1-y, Uy)C

International Nuclear Information System (INIS)

Koyama, Tadafumi; Yamawaki, Michio

1989-01-01

Vaporization thermodynamics of thorium-uranium mixed monocarbide phase (Th 1-y , U y )C was studied by mass spectrometric Knudsen effusion method for the compositions of (Th 0.9 , U 0.1 )C 0.855 , (Th 0.8 , U 0.2 )C 0.973 and (Th 0.6 , U 0.4 )C 0.973 . The partial vapor pressures of Th(g) and U(g) and activities of Th and U of these mixed monocarbides were determined at temperatures ranging from about 2000 to 2200 K. Further, the partial pressures of Th(g) and U(g) and activities of Th and U of the stoichiometric mixed monocarbides (Th 1-y , U y )C 1.00 were evaluated by compensating for the effect of carbon content. The Gibbs energies of formation of stoichiometric (Th 1-y , U y )C 1.00 were also evaluated. (orig.)

Influence of Radix scutellariae on Th1/Th2 cytokine balance in RU486-induced abortion in mice

Institute of Scientific and Technical Information of China (English)

ZHONG Xiuhui; SHI Wanyu; MA Aituan; WANG Xiaodan; ZHANG Jianlou; LI Xuezhong

2007-01-01

The aim of this study is to investigate the significance of Th1/Th2 cytokine balance in the uterus in the early embryo loss(or resorption),and to elucidate immunological modulation at the maternal-fetal interface with Chinese herbal medicine Radix scutellariae(Huang Qin)and its constituents(Baicalin and Baicalein).Mifepristone(RU486)was given via subcutaneous injection in the scapular area to induce abortion in mice at day 7 of gestation.The levels of uterine Thl cytokines(IFN-β,IL-2)and Th2 cytokines(IL-4,IL-10)were analyzed by enzyme-linked immunosorbent assay(ELISA),respectively.The mean values of Thl cytokines in the uterus of RU486-treated abortion mice were significantly higher(P＜0.05)than that of the control mice,but no significant difference was observed regarding to the contents of Th2 cytokines of different groups(P＞0.05).However,when the Radix scutellariae and its constituents were used to prevent RU486-induced abortion,the levels of IFN-γ and IL-2 decreased while that of IL-4 and IL-10 increased.The embryo loss induced by RU486 was closely related to the Th1/Th2 immune balance at the maternal-fetal interface.Radix scutellariae and its constituents have an anti-abortive effect through restoring the Th1/Th2 balance at the maternal-fetal interface.