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

Duhen, R;Glatigny, S;Arbelaez, CA;Blair, TC;Oukka, M;Bettelli, E;

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.