Aiolos promotes TH17 differentiation by directly silencing Il2 expression

IL-2 production is actively suppressed during TH17 differentiation. Quintana and colleagues show that the transcription factor Aiolos is induced by the transcription factors STAT3 and AhR and silences the Il2 locus. CD4+ interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are instrumental in the immune response to pathogens. However, an overactive TH17 response results in tissue inflammation and autoimmunity, and therefore it is important to identify the molecular mechanisms that control the development of TH17 cells. IL-2 suppresses such development, but how IL-2 production is actively suppressed during TH7 differentiation is not understood. Here we report that under TH17-polarizing conditions, the transcription factors STAT3 and AhR upregulated the expression of Aiolos, a member of the Ikaros family of transcription factors. Using Aiolos-deficient mice, we demonstrated that Aiolos silenced the Il2 locus, promoting TH17 differentiation in vitro and in vivo. Thus, we have identified a module in the transcriptional program of TH17 cells that actively limits IL-2 production and promotes their differentiation.