Transcription Factors and Th17 Cell Development in Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE), a widely studied animal model of human central nervous system demyelinating diseases such as multiple sclerosis, is a T-cell-mediated autoimmune disease involving effector T helper (Th) subsets such as Th1 and Th17. Recently, Th17 cells have been shown to play a major role in many autoimmune and other inflammatory diseases. The development of Th subsets is controlled by a complex network of cytoldnes and signaling and transcription molecules that act to augment the development of one cell type while restricting the development of other lineages. Here, we review the transcription factors (TFs) that are required for Th17 cell development in EAE and classify them into three types: major or essential such as ROR gamma t and STAT3, an array of helper factors that work in combination with or regulate the expression of the major factors, and regulatory TFs that attenuate the expression of Th17 genes. The plasticity of the Th17 cell lineage is also discussed in relation to the interaction of TFs that play a major role in the development of other Th or regulatory T cell (Treg) lineages such as T-bet and Foxp3 with the Th17 TFs.