实验性自身免疫性脑脊髓炎
免疫学
自身免疫
白细胞介素17
炎症
白细胞介素23
细胞因子
发病机制
自身免疫性疾病
生物
白细胞介素
免疫系统
抗体
作者
Melanie A. Kleinschek,Alexander M. Owyang,Barbara Joyce-Shaikh,Claire L. Langrish,Yi Chen,Daniel M. Gorman,Wendy M. Blumenschein,Terrill K. McClanahan,Frank Brombacher,Stephen D. Hurst,Robert A. Kastelein,J. Daniel
摘要
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–, IFNγ-, and TNF-producing T cells that invade the central nervous system. Neutralization of IL-17 but not IFNγ 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-1β, 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.
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