Central nervous system-targeted expression of the complement inhibitor sCrry prevents experimental allergic encephalomyelitis.
Central nervous system-targeted expression of the complement inhibitor sCrry prevents experimental allergic encephalomyelitis.
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DOI：
10.4049/jimmunol.163.12.6551
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发表时间：
1999-12
影响因子：
4.4
通讯作者：
N. Davoust;Serge Nataf;R. Reiman;Michael Holers;Iain L. Campbell;S. Barnum
中科院分区：
文献类型：
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作者：
N. Davoust;Serge Nataf;R. Reiman;Michael Holers;Iain L. Campbell;S. Barnum
虽然通常认为是T细胞驱动的自身免疫性疾病，但最近对多发性硬化症动物模型实验性过敏性脑脊髓炎（EAE）的研究表明先天免疫机制发挥重要作用。为了解决补体系统在这些疾病中发挥核心作用的可能性，我们开发了一种转基因小鼠，其具有星形胶质细胞靶向的补体激活的可溶性抑制剂补体受体相关蛋白y（sCrry）的产生。在这里，我们表明sCrry转基因小鼠要么完全免受EAE的影响，要么出现明显延迟的临床体征。这些结果表明，补体激活可能在疾病的发病机制中起着重要作用，补体介导的事件可能发生在EAE效应期的早期。此外，这项工作强调了体液免疫在放大T细胞启动的致病过程中的重要性。
Although generally thought of as a T cell-driven autoimmune disease, recent studies in experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis, suggest a significant role for innate immune mechanisms. To address the possibility that the complement system plays a central role in these diseases, we developed a transgenic mouse with astrocyte-targeted production of a soluble inhibitor of complement activation, complement receptor-related protein y (sCrry). Here, we show that sCrry transgenic mice are either fully protected against EAE or develop significantly delayed clinical signs. These results indicate that complement activation may have an essential role in the pathogenesis of the disease and that complement-mediated events may occur early during the effector phase of EAE. Furthermore, this work underscores the importance of humoral immunity in amplifying a T cell-initiated pathogenic process.