Induction of regulatory Tr1 cells and inhibition of TH17 cells by IL-27

Accumulating evidence indicates that IL-27, a member of the IL-12 family of cytokines, alleviates the severity of autoimmune diseases in both mice and men. The IL-27-induced activation of signal transducer and activator of transcription (Stat)1 and Stat3 promotes the generation of IL-10- producing type 1 regulatory T (Tr1) cells that inhibit effector T cells. In addition, IL-27 also suppresses the development of pathogenic IL-17-producing CD4+ T cells (TH17) cells suggesting that pharmacological manipulations of IL-27 signaling pathway could be exploited therapeutically in regulating tissue inflammation. Here, we review how IL-27 controls inflammation through the regulation of Tr1 and TH17 responses.

► IL-27 controls autoimmune responses by promoting Tr1 cells and inhibiting TH17 cells. ► IL-27 triggers Stat1 and Stat3 signaling. ► IL-27 induces Maf and AhR that control IL-10 secretion from Tr1 cells. ► Stat1 activation represses TH17 cells and induces Tr1 cells. ► IL-27 alleviates human autoimmune diseases.