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The death receptor Fas removes activated lymphocytes through apoptosis. Previous transcriptional profiling predicted that Fas positively regulates interleukin-17 (IL-17)-producing T helper 17 (Th17) cells. Here, we demonstrate that Fas promoted the generation and stability of Th17 cells and prevented their differentiation into Th1 cells. Mice with T-cell- and Th17-cell-specific deletion of Fas were protected from induced autoimmunity, and Th17 cell differentiation and stability were impaired. Fas-deficient Th17 cells instead developed a Th1-cell-like transcriptional profile, which a new algorithm predicted to depend on STAT1. Experimentally, Fas indeed bound and sequestered STAT1, and Fas deficiency enhanced IL-6-induced STAT1 activation and nuclear translocation, whereas deficiency of STAT1 reversed the transcriptional changes induced by Fas deficiency. Thus, our computational and experimental approach identified Fas as a regulator of the Th17-to-Th1 cell balance by controlling the availability of opposing STAT1 and STAT3 to have a direct impact on autoimmunity.Fas promotes the in vivo pathogenicity of T helper 17 cellsFas promotes the stability of T helper 17 cells by preventing STAT1 activationFas regulates the STAT1 versus STAT3 balance by binding and sequestering STAT1Fas is a cell-intrinsic regulator of competing T helper cell differentiation programsFas is a well-known death receptor that can also mediate non-apoptotic functions. Meyer zu Horste et al. demonstrate that Fas promotes the stability and pathogenicity of T helper 17 cells by sequestering and inhibiting the activation of STAT1 and regulating the availability of opposing STAT1 and STAT3.