Cutting edge: the pathogenicity of IFN-?-producing Th17 cells is independent of T-bet.

ABSTRACT: During the development of experimental autoimmune encephalomyelitis (EAE), the proportion of pathogenic and myelin-specific cells within CNS-infiltrating cytokine-producing Th cells is unknown. Using an IL-17A/IFN-? double reporter mouse and I-A(b)/myelin oligodendrocyte glycoprotein 38-49 tetramer, we show in this study that IL-17(+)IFN-?(+) Th cells, which are expanded in the CNS during EAE, are highly enriched in myelin oligodendrocyte glycoprotein-specific T cells. We further demonstrate that IL-23 is essential for the generation and expansion of IFN-?-producing Th17 cells independently of the Th1-associated transcription factors T-bet, STAT1, and STAT4. Furthermore, Th17 and IL-17(+)IFN-?(+) Th cells can induce CNS autoimmunity independently of T-bet. Whereas T-bet is crucial for Th1-mediated EAE, it is dispensable for Th17 cell-mediated autoimmunity. Our results suggest the existence of different epigenetic programs that regulate IFN-? expression in Th1 and Th17 cells.

SUBMITTER: Duhen R 

PROVIDER: S-EPMC3633668 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature