A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis

摘要: It was recently demonstrated that interleukin (IL)-23–driven IL-17–producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases. We show the induction of antigen-specific ThIL-17 cells, but not helper (Th)1 or Th2 by immunization with antigens and adjuvants is abrogated IL-1 receptor type I–deficient (IL-1RI−/−) mice. Furthermore, incidence experimental encephalomyelitis (EAE) significantly lower IL-1RI−/− compared wild-type mice, this correlated a failure to induce autoantigen-specific whereas Th1 responses substantially different. However, EAE induced mice adoptive transfer from EAE. IL-23 alone did IL-17 production IL-23–induced enhanced IL-1α IL-1β, even absence cell stimulation. demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor κB, novel protein kinase C isoforms IL-1– IL-23–mediated production. Tumor necrosis α also synergized enhance production, dependent. Our findings functions upstream promote pathogenic