| First Author | Kleinschek MA | Year | 2007 |
| Journal | J Exp Med | Volume | 204 |
| Issue | 1 | Pages | 161-70 |
| PubMed ID | 17200411 | Mgi Jnum | J:125296 |
| Mgi Id | MGI:3758138 | Doi | 10.1084/jem.20061738 |
| Citation | Kleinschek MA, et al. (2007) IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med 204(1):161-70 |
| abstractText | Interleukin (IL)-25 is a member of the IL-17 family of cytokines. However, unlike the other members of this family, IL-25 promotes T helper (Th) 2 responses. We now show that IL-25 also regulates the development of autoimmune inflammation mediated by IL-17-producing T cells. We have generated IL-25-deficient (il25-/-) mice and found that they are highly susceptible to experimental autoimmune encephalomyelitis (EAE). The accelerated disease in the il25-/- mice is associated with an increase of IL-23 in the periphery and a subsequent increase in the number of inflammatory IL-17-, IFNgamma-, and TNF-producing T cells that invade the central nervous system. Neutralization of IL-17 but not IFNgamma in il25-/- mice prevented EAE, suggesting that IL-17 is a major disease-promoting factor. IL-25 treatment at several time points during a relapse-remitting model or chronic model of EAE completely suppressed disease. IL-25 treatment induced elevated production of IL-13, which is required for suppression of Th17 responses by direct inhibition of IL-23, IL-1beta, and IL-6 expression in activated dendritic cells. Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity. |
