I[kgr]B[zgr] regulates TH17 development by cooperating with ROR nuclear receptors

摘要: The development of interleukin (IL)-17-producing T cells (TH17 cells) is shown to require the transcription factor IκBζ in addition ROR nuclear receptors. cooperates with factors through binding upstream conserved non-coding sequence CNS2, and mice deficient for are resistant induction experimental autoimmune encephalomyelitis. work highlights transcriptional mechanisms involved TH17 suggests novel therapeutic approaches disease. Interleukin-17-producing helper (TH17) a distinct T-cell subset characterized by its role Here it that requires IκBζ, as well receptors family. Mice lacking have defect study points some new potential molecular targets drugs treat Interleukin pathological diseases1,2,3. IL-6 transforming growth factor-β (TGF-β) induce development, which orphan receptors, RORγt RORα, an indispensable role4,5,6. However, absence TGF-β, ectopic expression or RORα leads only modest IL-17 production5,7,8. we identify IκB family member, (encoded Nfkbiz gene), required mice. naive CD4+ together potently induces even TGF-β. Notably, Nfkbiz-/- resistance encephalomyelitis (EAE). T-cell-intrinsic function was clearly demonstrated EAE Rag2-/- into were transferred. In cooperation enhances Il17a directly regulatory region gene. This provides evidence underlying basis strategy against