Transcriptional regulation of T helper 17 cell differentiation

The third lineage of T helper subsets, Th17, has recently been identified as an IL- 17-producing CD4+ Th cell, and its functions and regulatory mechanisms have been extensively characterized in immune responses. Functional studies have provided evidence that Th17 cells are important for the modulation of autoimmune responses, such as chronic asthma, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis. Murine Th17 cell differentiation is enhanced by the coordinated functions of distinct cytokines including TGFbeta, IL-6, IL-21, and IL-23, whereas IL-2, IL-4, IFNgamma, and IL-27 inhibit its differentiation. In addition, Th17 cells are controlled by several transcription factors such as RORgammat, IRF4, BATF, FoxP3, T-bet, PPARgamma, E-FABP, and SOCSs. This review focuses on the functions and regulatory mechanisms of several transcription factors in the control of Th17 cell differentiation.