The transcription factor c-Maf is a positive regulator of IL-10 with context-specific roles in CD4+ T cell effector function and in vivo consequences [RNA-seq in vitro]

CD4+ T cells differentiate into distinct subsets which produce unique patterns of cytokines to eradicate pathogens, alongside IL-10 which controls immune pathology. How Il10 expression is regulated alongside the subset-specific cytokines is unclear. Using transcriptional and epigenomic profiling of CD4+ T cells from TH1 (malaria), TH2 (allergy) and TH17 (autoimmunity) disease models, we show here that c-Maf, identified as the top candidate regulator of IL-10, directly induces IL-10 across all CD4+ T cell subsets, controlling pathology in TH1 and TH2-type responses. We also report direct negative effects of c-Maf on Il2 explaining the increased Foxp3+Tregs, and direct positive effects on Rorc, as mechanisms for the decreased pathology seen in the TH17 disease model in the absence of c-Maf. Thus, c-Maf has broad yet context specific roles in directly and indirectly regulating gene expression, allowing each type of T effector immune response to occur effectively yet in a controlled fashion. Overall design: RNA-Seq analysis, in 2-3 biological replicates, of in vitro differentiated CD4+ Th cells and ex vivo Treg cells