The role of Stat4 in IL-23-dependent IL-17 production (114.2)

TL;DRAbstract

Abstract Signal transducers and activators of transcription (STAT) proteins are induced upon cytokine and growth factor stimulation and play a pivotal role in immune and inflammatory responses. Stat4 is a critical mediator of inflammatory immunity and is required for all known IL-12 biological responses, including the induction of IFN-γ and development of Th1 cells. IL-23, an IL-12-related cytokine, also induces Stat4 activation, which may be important for optimal IL-17 secretion from CD4+ T cells. We further characterized the requirement for Stat4 in IL-23-mediated cytokine production using cells from Stat4-deficient mice. Stat4-deficient CD4+ T cells display reduced cytokine-induced IL-17 production in comparison to control cells, and this phenotype is most prominent in IL-23-primed memory CD4+ T cells. Furthermore, innate IL-17-producing cells, such as γδ T cells, natural killer T (NKT) cells and natural killer (NK) cells display distinct dependence on Stat4 activation for IL-17 pro

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