Critical Role of TCF-1 in Repression of the IL-17 Gene

摘要: Overwhelming activation of IL-17, a gene involved in inflammation, leads to exaggerated Th17 responses associated with numerous autoimmune conditions, such as experimental encephalomyelitis (EAE). Here we show that TCF-1 is critical factor repress IL-17 locus by chromatin modifications during T cell development. Deletion resulted increased expression both thymus and peripheral cells, which led enhanced differentiation. As result, TCF-1-/- mice were susceptible Th17-dependent EAE induction. Rag1-/- reconstituted cells also EAE, indicating intrinsically required IL-17. However, wild-type or dominant negative did not interfere differentiation mature cells. Furthermore, could restore levels, cannot affect production at the stage. This supported normal up-regulation factors known regulate differentiation, including RORγt Stat3. We observed hyperacetylation together trimethylation Lys-4 thymocytes, two epigenetic an open active state gene. Such preserved even when migrated out thymus. Therefore, mediates process via TCF-1-mediated repression for generate balanced immune responses.