Interferon-β is a key regulator of proinflammatory events in experimental autoimmune encephalomyelitis
Interferon-β is a key regulator of proinflammatory events in experimental autoimmune encephalomyelitis
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DOI：
10.1177/1352458510381259
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发表时间：
2010-12-01
影响因子：
5.8
通讯作者：
Fish, E. N.
中科院分区：
文献类型：
--
作者：
Galligan, C. L.;Pennell, L. M.;Fish, E. N.
背景资料：干扰素（IFN）-β是治疗复发缓解型多发性硬化症的有效方法，但其作用机制仍不明确。目的：我们的目的是描述IFN-β在实验性自身免疫性脑脊髓炎（EAE）中的免疫调节作用。在IFN-β存在或不存在的情况下，用髓鞘少突胶质细胞糖蛋白肽免疫IFN-β（+/+）和IFN-β（-/-）小鼠，以诱导EAE。在发病率、发病时间、临床评分和受影响小鼠的脑、脾和淋巴结中的免疫细胞活化的背景下监测疾病发病机制。与IFN-β（+/+）小鼠相比，IFN-β（-/ -）小鼠表现出更早的EAE发作和更快的进展，浸润受影响大脑的CD 11b（+）白细胞数量增加，中枢神经系统和引流淋巴结中Th 17细胞百分比增加。IFN-β治疗延迟了疾病发作并降低了疾病严重程度。体外实验表明，缺乏IFN-β导致自身反应性T细胞的产生增加，这可能是CD 4（+）T细胞和抗原呈递树突状细胞中缺乏IFN-β调节事件的结果。IFN-β处理的骨髓巨噬细胞（CD 11b（+））的基因表达分析确定调制影响T细胞增殖和Th 17分化的基因。结论：我们得出结论，IFN-β的行为，以抑制自身免疫诱导的Th 17细胞在疾病的发展过程中，以及调制促炎介质的产生。
Background: Interferon (IFN)-beta is an effective therapy for relapsing-remitting multiple sclerosis, yet its mechanism of action remains ill-defined.Objectives: Our objective was to characterize the role of IFN-beta in immune regulation in experimental autoimmune encephalomyelitis (EAE).Methods: IFN-beta (+/+) and IFN-beta(-/-) mice were immunized with myelin oligodendrocyte glycoprotein peptide in the presence or absence of IFN-beta, to induce EAE. Disease pathogenesis was monitored in the context of incidence, time of onset, clinical score, and immune cell activation in the brains, spleens and lymph nodes of affected mice.Results: Compared with IFN-beta(+/+) mice, IFN-beta(-/ -) mice exhibited an earlier onset and a more rapid progression of EAE, increased numbers of CD11b(+) leukocytes infiltrating affected brains and an increased percentage of Th17 cells in the central nervous system and draining lymph nodes. IFN-beta treatment delayed disease onset and reduced disease severity. Ex vivo experiments revealed that the lack of IFN-beta results in enhanced generation of autoreactive T cells, a likely consequence of the absence of IFN-beta-regulated events in both the CD4(+) T cells and antigen-presenting dendritic cells. Gene expression analysis of IFN-beta-treated bone marrow macrophages (CD11b (+)) identified modulation of genes affecting T cell proliferation and Th17 differentiation.Conclusions: We conclude that IFN-beta acts to suppress the generation of autoimmune-inducing Th17 cells during the development of disease as well as modulating pro-inflammatory mediators.