ArrayExpress Uploader06183No_CytokineNo_CytokineIL6_IL1IL6_IL1IL6_IL1_IL23IL6_IL1_IL23IL6_IL1_TGFBIL6_IL1_TGFBIL6_TGFB_TGFBRiIL6_TGFBarrayexpress_sid6CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17...20962846E-GEOD-23505/profile/8773/arrayexpressuploader110celldiseaseencephalomyelitisinterleukinDec.12, 2014Falseenhanced-pathogenicity-of-th17-cells-generated-inE-GEOD-23505_A-AFFY-45Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-β SignalingNov.11, 2014CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+Rorγt+ 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-β1 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. Mouse T helper 17 cell differentiation with or without TGFBhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-23505mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-23505/samples/