SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth.
Abstract Activation of the transcription factor PPARγ by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARγ are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARγ. SOCS3 promoter binding and gene transactivation by PPARγ was associated with a repression in differentiation of proinflammatory T-helper (TH)17 cells. Accordingly, TH17 cells induced in vitro displayed increased SOCS3 expression and diminished capacity to produce interleukin (IL)-17 following activation of PPARγ by DHA. Furthermore, naïve CD4…
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 (T(H)17) 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 T…