GSE23681
Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-ß Signaling: ChIPSeq
CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity. Crucial for T helper17 (Th17) cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-ß1 have been argued to be the factors responsible for initiating specification. Herein, we show that Th17 differentiation occurs in the absence of TGF-ß signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1ß effectively induced IL-17 production in naïve precursors, independently of TGF-ß. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-ß1, allowing the generation of cells that co-expressed Ror?t and T-bet. T-bet+Ror?t+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-ß1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies. Overall design: Examination of Stat3 binding and H3K4me and H3Ac in helper T cells.