Interleukin-19 alleviates experimental autoimmune encephalomyelitis by attenuating antigen-presenting cell activation
Interleukin-19 alleviates experimental autoimmune encephalomyelitis by attenuating antigen-presenting cell activation
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DOI：
10.1101/2020.07.15.204826
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发表时间：
2020-07
期刊：
影响因子：
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通讯作者：
H. Horiuchi;Bijay Parajuli;Hiroyasu Komiya;Y. Ogawa;Shijie Jin;Keita Takahashi;Y. Azuma;F. Tanaka;A. Suzumura;H. Takeuchi
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文献类型：
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作者：
H. Horiuchi;Bijay Parajuli;Hiroyasu Komiya;Y. Ogawa;Shijie Jin;Keita Takahashi;Y. Azuma;F. Tanaka;A. Suzumura;H. Takeuchi
白细胞介素-19（IL-19）在多种炎性疾病中作为抗炎细胞因子起作用。多发性硬化（MS）是中枢神经系统的主要神经炎性疾病，但IL-19如何参与MS发病机制仍不清楚。在这里，我们证明，IL-19缺乏症通过促进IL-17产生辅助性T细胞（Th 17细胞）浸润到中枢神经系统，从而导致实验性自身免疫性脑脊髓炎（EAE），MS的小鼠模型。此外，IL-19缺陷型脾巨噬细胞表达升高水平的主要组织相容性复合物II类、共刺激分子和Th 17细胞分化相关细胞因子，如IL-1β、IL-6、IL-23、TGF-β1和TNF-α。这些观察结果表明，IL-19通过抑制巨噬细胞抗原呈递、Th 17细胞扩增和随后的炎症反应在抑制MS发病机制中起关键作用。此外，用IL-19治疗显著消除EAE。我们的数据表明，IL-19可以为MS患者提供显著的治疗益处。
Interleukin-19 (IL-19) acts as an anti-inflammatory cytokine in various inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system, but it remains uncertain how IL-19 contributes to MS pathogenesis. Here, we demonstrate that IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by promoting IL-17–producing helper T cell (Th17 cell) infiltration into the central nervous system. In addition, IL-19–deficient splenic macrophages expressed elevated levels of major histocompatibility complex class II, co-stimulatory molecules, and Th17 cell differentiation–associated cytokines such as IL-1β, IL-6, IL-23, TGF-β1, and TNF-α. These observations indicated that IL-19 plays a critical role in suppression of MS pathogenesis by inhibiting macrophage antigen presentation, Th17 cell expansion, and subsequent inflammatory responses. Furthermore, treatment with IL-19 significantly abrogated EAE. Our data suggest that IL-19 could provide significant therapeutic benefits in patients with MS.