Characterization of the interaction between astrocytes and encephalitogenic lymphocytes during the development of experimental autoimmune encephalitomyelitis (EAE) in mice
Characterization of the interaction between astrocytes and encephalitogenic lymphocytes during the development of experimental autoimmune encephalitomyelitis (EAE) in mice
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DOI：
10.1111/j.1365-2249.2012.04661.x
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发表时间：
2012-12
影响因子：
4.6
通讯作者：
Jinfeng Yang;H. Tao;Ying Liu;Xiao-xia Zhan;Yu Liu;Xinyue Wang;J. Wang;Lili Mu;L. L. Yang-L.;Zhongming Gao;Qingfei Kong;Guangyou Wang;Junwei Han;Bo Sun;Hulun Li;Hulun Li
中科院分区：
文献类型：
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作者：
Jinfeng Yang;H. Tao;Ying Liu;Xiao-xia Zhan;Yu Liu;Xinyue Wang;J. Wang;Lili Mu;L. L. Yang-L.;Zhongming Gao;Qingfei Kong;Guangyou Wang;Junwei Han;Bo Sun;Hulun Li;Hulun Li
与多发性硬化（MS）的发展相关的致病机制的性质长期以来一直存在争议。然而，进行了有限的研究，以确定浸润淋巴细胞和中枢神经系统（CNS）的驻留细胞之间的相互作用。本报告中提供的数据描述了星形胶质细胞介导的髓鞘少突胶质细胞糖蛋白（MOG）35-55特异性淋巴细胞反应改变的新作用，该反应在实验性自身免疫性脑脊髓炎（EAE）发生期间引起。体外研究表明，星形胶质细胞抑制MOG 35 -55特异性淋巴细胞的增殖和干扰素（IFN）-γ、白细胞介素（IL）-4、IL-17和转化生长因子（TGF）-β分泌水平，星形胶质细胞IL-27中和可改善这种效应。然而，当星形胶质细胞用IFN-γ预处理时，它们可以促进MOG 35 -55特异性淋巴细胞的增殖和分泌水平，与星形胶质细胞本身上的主要组织相容性复合物（MHC）-II的明显表达相一致。定量聚合酶链反应（qPCR）表明，脊髓中IL-27的产生在初始阶段达到最高水平。相反，脊髓中IFN-γ的产生在高峰期最高。脊髓中MHC-II表达的定量分析表明，MHC-II表达与IFN-γ产生之间呈正相关。此外，星形胶质细胞MHC-II表达水平与脊髓中IFN-γ的产生呈正相关。这些结果表明，星形胶质细胞可能是EAE的抑制剂和促进剂。星形胶质细胞在EAE的初始阶段通过分泌IL-27阻止MOG 35 -55特异性淋巴细胞功能。然后，在脊髓中存在较高的IFN-γ水平的情况下，星形胶质细胞转化为抗原呈递细胞。这种转化可能促进病理损害的进展，导致EAE严重程度达到高峰。
The nature of pathogenic mechanisms associated with the development of multiple sclerosis (MS) have long been debated. However, limited research was conducted to define the interplay between infiltrating lymphocytes and resident cells of the central nervous system (CNS). Data presented in this report describe a novel role for astrocyte‐mediated alterations to myelin oligodendrocyte glycoprotein (MOG)35–55‐specific lymphocyte responses, elicited during the development of experimental autoimmune encephalitomyelitis (EAE). In‐vitro studies demonstrated that astrocytes inhibited the proliferation and interferon (IFN)‐γ, interleukin (IL)‐4, IL‐17 and transforming growth factor (TGF)‐β secretion levels of MOG35–55‐specific lymphocytes, an effect that could be ameliorated by astrocyte IL‐27 neutralization. However, when astrocytes were pretreated with IFN‐γ, they could promote the proliferation and secretion levels of MOG35–55‐specific lymphocytes, coinciding with apparent expression of major histocompatibility complex (MHC)‐II on astrocytes themselves. Quantitative polymerase chain reaction (qPCR) demonstrated that production of IL‐27 in the spinal cord was at its highest during the initial phases. Conversely, production of IFN‐γ in the spinal cord was highest during the peak phase. Quantitative analysis of MHC‐II expression in the spinal cord showed that there was a positive correlation between MHC‐II expression and IFN‐γ production. In addition, astrocyte MHC‐II expression levels correlated positively with IFN‐γ production in the spinal cord. These findings suggested that astrocytes might function as both inhibitors and promoters of EAE. Astrocytes prevented MOG35–55‐specific lymphocyte function by secreting IL‐27 during the initial phases of EAE. Then, in the presence of higher IFN‐γ levels in the spinal cord, astrocytes were converted into antigen‐presenting cells. This conversion might promote the progression of pathological damage and result in a peak of EAE severity.