RGC-32 is essential for TGF-β mediated Th17 cell differentiation (LYM3P.728)
Journal of Immunology(2014)
摘要
Abstract Our group has cloned and characterized the Response Gene to Complement (RGC)-32 which is induced by C5b-9 and exerts an important role in cell cycle activation via cyclin B1-CDC2 activation and Akt phosphorylation. RGC-32 is also a downstream target of TGF-β and plays a role in fibrogenesis. As Th17 and induced T regulatory cells (iTreg) differentiate under the control of TGF-β, we determined whether RGC-32 plays a role in this process using RGC-32 KO mice generated in our lab. RGC-32 was not required for peripheral T cell homeostasis as we observed normal cellularity, T cell subset composition and phenotypic markers. However, RGC-32 KO CD4+ T cells failed to differentiate normally to Th17 lineage as they exhibited a significant reduction in IL-17 and RORγt mRNA and protein expression in vitro and a decreased proportion of IL-17+ cells in lamina propria lymphocytes in vivo. The defect in IL-17 expression appeared to be mediated by decreased expression of IL-6R and TGF-βRI at baseline and under Th17 conditions and was not restored by IL-2 inhibition. A trend for increased iTreg differentiation was noted in RGC-32 KO CD4+ T cells under Treg skewing conditions but the difference was not statistically significant. Differentiation of CD4+ T cells into Th1 cells was decreased in RGC-32 KO mice while Th2 cells developed normally. These results suggest that RGC-32 is a novel mediator of Th17 differentiation in vitro and in vivo through modulation of IL-6R and TGF-βRI expression.
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关键词
th17 cell differentiation
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