Molecular mechanisms of T helper 17 cell differentiation: Emerging roles for transcription cofactors

T helper 17 (Th17) cells, characterized by secretion of IL-17 and IL-17F, are a specialized CD4⁺ effector T cell lineage that not only facilitates host defense against pathogen infection and maintenance of mucosal barrier, but also potently induces tissue inflammation and autoimmune diseases. Since its discovery in 2005, the developmental program of Th17 cells has been characterized, which involves a number of key cytokines, transcription factors and multiple layers of epigenetic modifications. However, how these mechanisms integrate into the complex regulatory network in Th17 cells has not been well defined. Emerging evidences have revealed essential roles of cofactors in controlling chromosome accessibilities and activities of Th17-specific transcription factors. Moreover, cofactors also act as critical signaling integrators to coordinate multiple signaling pathways and transcriptional programs. Deficiency or dysregulation of these cofactors results in defects in Th17 responses and induction of associated autoimmune diseases. Our lab has recently reported several important cofactors in Th17 cells. Here we summarize our findings regarding this new scenario of developmental regulation of Th17 cells. These findings may benefit the development of innovative strategies to treat autoimmune diseases.