Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination.
Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination.
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DOI：
10.1186/s12974-017-0899-1
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发表时间：
2017-06-24
影响因子：
9.3
通讯作者：
Owens T
中科院分区：
文献类型：
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作者：
Berg CT;Khorooshi R;Asgari N;Owens T
对髓鞘少突胶质细胞糖蛋白（MOG）具有特异性的抗体与多发性硬化和相关疾病有关。抗MOG抗体在原发性脱髓鞘病理学中的致病重要性仍不清楚。本研究的目的是研究抗MOG抗体的施用是否足以用于脱髓鞘，并确定I型干扰素（IFN）信号传导是否在抗MOG抗体介导的病理学中起类似作用，如已经显示的视神经肌萎缩样病理学。将纯化的IgG 2a单克隆抗MOG抗体和小鼠补体立体定向注射到具有和不具有预先建立的实验性自身免疫性脑脊髓炎（EAE）的野生型和I型IFN受体缺陷小鼠（IFNAR 1-KO）的胼胝体中。抗-MOG诱导野生型小鼠胼胝体中补体依赖性脱髓鞘，而在接受对照IgG 2a的小鼠中未发生。活化补体的沉积与脱髓鞘一致，并且在IFNAR 1-KO小鼠中这显著减少。在EAE症状发作时共注射抗MOG和补体在野生型和IFNAR 1-KO小鼠中诱导了相似水平的胼胝体脱髓鞘。抗MOG抗体和补体足以诱导胼胝体脱髓鞘，病理学依赖于I型IFN。在IFNAR 1-KO小鼠中诱导EAE克服了I型IFN对抗MOG和补体介导的脱髓鞘的依赖性。本文的在线版本（doi：10.1186/s12974-017-0899-1）包含补充材料，可供授权用户使用。
Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. The objective of this study is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology. Purified IgG2a monoclonal anti-MOG antibody and mouse complement were stereotactically injected into the corpus callosum of wild-type and type I IFN receptor deficient mice (IFNAR1-KO) with and without pre-established experimental autoimmune encephalomyelitis (EAE). Anti-MOG induced complement-dependent demyelination in the corpus callosum of wild-type mice and did not occur in mice that received control IgG2a. Deposition of activated complement coincided with demyelination, and this was significantly reduced in IFNAR1-KO mice. Co-injection of anti-MOG and complement at onset of symptoms of EAE induced similar levels of callosal demyelination in wild-type and IFNAR1-KO mice. Anti-MOG antibody and complement was sufficient to induce callosal demyelination, and pathology was dependent on type I IFN. Induction of EAE in IFNAR1-KO mice overcame the dependence on type I IFN for anti-MOG and complement-mediated demyelination. The online version of this article (doi:10.1186/s12974-017-0899-1) contains supplementary material, which is available to authorized users.