IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis
IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis
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DOI：
10.4049/jimmunol.177.1.566
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Iwakura, Yoichiro
中科院分区：
文献类型：
--
作者：
Komiyama, Yutaka;Nakae, Susumu;Iwakura, Yoichiro
IL-17是一种促炎细胞因子，其激活T细胞和其他免疫细胞以产生多种细胞因子、趋化因子和细胞粘附分子。这种细胞因子在接触性皮炎、哮喘和类风湿性关节炎患者的血清和/或组织中增加。我们先前证明IL-17参与小鼠自身免疫性关节炎和接触性、迟发性和气道超敏反应的发展。由于IL-17的表达在多发性硬化中也增加，我们使用IL-17（-/-）鼠疾病模型检查了这种细胞因子在这些疾病中的参与。我们发现，实验性自身免疫性脑脊髓炎（EAE）的发展，多发性硬化的啮齿动物模型，在IL-17（-/-）小鼠中被显着抑制;这些动物表现出延迟发作，降低最大严重程度评分，改善组织学变化，并早期恢复。在致敏后，IL-17-/-小鼠中针对髓鞘少突胶质细胞糖蛋白的T细胞致敏降低。在用髓磷脂digodendrocyte glycopritein处理后，IL-17的主要产生者是CD 4（+）T细胞而不是CD 8（+）T细胞，并且IL-17（-/-）CD 4（+）T细胞的过继转移在受者体内无效地诱导EAE。值得注意的是，产生IL-17的T细胞在IFN-γ（-/-）细胞中增加，而产生IFN-γ的细胞在IL-17（-/-）细胞中增加，表明IL-17和IFN-γ相互调节IFN-γ和IL-17的产生。这些观察结果表明，IL-17而不是IFN-γ在EAE的发展中起着至关重要的作用。
IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17(-/-) murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17(-/-) mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17-/- mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4(+) T cells rather than CD8(+) T cells, and adoptive transfer of IL-17(-/-) CD4(+) T cells inefficiently induced EAE in recipient In ice. Notably, IL-17-producing T cells were increased in IFN-gamma(-/-) cells, while IFN-gamma-producing cells were increased in IL-17(-/-) cells, suggesting that IL-17 and IFN-gamma mutually regulate IFN-gamma and IL-17 production. These observations indicate that IL-17 rather than IFN-gamma plays a crucial role in the development of EAE.