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dc.contributor.authorYang, Jianjunen_US
dc.contributor.authorZhang, Ruihuaen_US
dc.contributor.authorLu, Gemingen_US
dc.contributor.authorShen, Yuen_US
dc.contributor.authorPeng, Liangen_US
dc.contributor.authorZhu, Chenen_US
dc.contributor.authorCui, Miaoen_US
dc.contributor.authorWang, Weidongen_US
dc.contributor.authorArnaboldi, Paulen_US
dc.contributor.authorTang, Mengen_US
dc.contributor.authorGupta, Monicaen_US
dc.contributor.authorQi, Chen-Fengen_US
dc.contributor.authorJayaraman, Padminien_US
dc.contributor.authorZhu, Hongfaen_US
dc.contributor.authorJiang, Boen_US
dc.contributor.authorChen, Shu-hsiaen_US
dc.contributor.authorHe, John Cijiangen_US
dc.contributor.authorTing, Adrian T.en_US
dc.contributor.authorZhou, Ming-Mingen_US
dc.contributor.authorKuchroo, Vijay K.en_US
dc.contributor.authorMorse, Herbert C.en_US
dc.contributor.authorOzato, Keikoen_US
dc.contributor.authorSikora, Andrew G.en_US
dc.contributor.authorXiong, Huabaoen_US
dc.date.accessioned2014-03-11T13:26:28Z
dc.date.issued2013en_US
dc.identifier.citationYang, J., R. Zhang, G. Lu, Y. Shen, L. Peng, C. Zhu, M. Cui, et al. 2013. “T cell–derived inducible nitric oxide synthase switches off TH17 cell differentiation.” The Journal of Experimental Medicine 210 (7): 1447-1462. doi:10.1084/jem.20122494. http://dx.doi.org/10.1084/jem.20122494.en
dc.identifier.issn0022-1007en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879570
dc.description.abstractRORγt is necessary for the generation of TH17 cells but the molecular mechanisms for the regulation of TH17 cells are still not fully understood. We show that activation of CD4+ T cells results in the expression of inducible nitric oxide synthase (iNOS). iNOS-deficient mice displayed enhanced TH17 cell differentiation but without major effects on either TH1 or TH2 cell lineages, whereas endothelial NOS (eNOS) or neuronal NOS (nNOS) mutant mice showed comparable TH17 cell differentiation compared with wild-type control mice. The addition of N6-(1-iminoethyl)-l-lysine dihydrochloride (L-NIL), the iNOS inhibitor, significantly enhanced TH17 cell differentiation, and S-nitroso-N-acetylpenicillamine (SNAP), the NO donor, dose-dependently reduced the percentage of IL-17–producing CD4+ T cells. NO mediates nitration of tyrosine residues in RORγt, leading to the suppression of RORγt-induced IL-17 promoter activation, indicating that NO regulates IL-17 expression at the transcriptional level. Finally, studies of an experimental model of colitis showed that iNOS deficiency results in more severe inflammation with an enhanced TH17 phenotype. These results suggest that NO derived from iNOS in activated T cells plays a negative role in the regulation of TH17 cell differentiation and highlight the importance of intrinsic programs for the control of TH17 immune responses.en
dc.language.isoen_USen
dc.publisherThe Rockefeller University Pressen
dc.relation.isversionofdoi:10.1084/jem.20122494en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698516/pdf/en
dash.licenseLAAen_US
dc.titleT cell–derived inducible nitric oxide synthase switches off TH17 cell differentiationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalThe Journal of Experimental Medicineen
dash.depositing.authorZhu, Chenen_US
dc.date.available2014-03-11T13:26:28Z
dc.identifier.doi10.1084/jem.20122494*
dash.authorsorderedfalse
dash.contributor.affiliatedZhu, Chen
dash.contributor.affiliatedKuchroo, Vijay


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