Interleukin-17A (IL-17A) is a major mediator of tissue inflammation in many autoimmune diseases. Anti-IL-17A is an effective treatment for psoriasis and is showing promise in clinical trials in multiple sclerosis. In this study, we find that IL-17A-defective mice or mice treated with anti-IL-17A at induction of experimental autoimmune encephalomyelitis (EAE) are resistant to disease and have defective priming of IL-17-secreting γδ T (γδT17) cells and Th17 cells. However, T cells from Il17a-/- mice induce EAE in wild-type mice following in vitro culture with autoantigen, IL-1β, and IL-23. Furthermore, treatment with IL-1β or IL-17A at induction of EAE restores disease in Il17a-/- mice. Importantly, mobilization of IL-1β-producing neutrophils and inflammatory monocytes and activation of γδT17 cells is reduced in Il17a-/- mice. Our findings demonstrate that a key function of IL-17A in central nervous system (CNS) autoimmunity is to recruit IL-1β-secreting myeloid cells that prime pathogenic γδT17 and Th17 cells.

中文翻译：

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白细胞介素17A通过招募可促进病原性T细胞的产生IL-1β的髓样细胞，在自身免疫中起主要作用。

白介素-17A（IL-17A）是许多自身免疫性疾病中组织炎症的主要介质。抗IL-17A是治疗牛皮癣的有效方法，在多发性硬化症的临床试验中显示出希望。在这项研究中，我们发现IL-17A缺陷型小鼠或在实验性自身免疫性脑脊髓炎（EAE）诱导下用抗IL-17A治疗的小鼠对疾病具有抵抗力，并具有分泌IL-17的γδT（γδT17）引发缺陷细胞和Th17细胞。然而，在用自身抗原，IL-1β和IL-23进行体外培养后，来自Il17a-/-小鼠的T细胞在野生型小鼠中诱导了EAE。此外，在诱导EAE时用IL-1β或IL-17A治疗可恢复II17a-/-小鼠的疾病。重要的是，在II17a-/-小鼠中减少了产生IL-1β的嗜中性白细胞和炎性单核细胞的动员以及γδT17细胞的活化。