Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system
Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system
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DOI：
10.1038/nm831
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发表时间：
2003-03-01
期刊：
影响因子：
82.9
通讯作者：
Jiang, H
中科院分区：
文献类型：
--
作者：
Yan, SS;Wu, ZY;Jiang, H
多发性硬化（MS）是中枢神经系统（CNS）的破坏性神经炎性病症，其中与髓鞘的主要组分反应的T细胞具有中心作用。晚期糖基化终末产物受体（receptor for advanced glycation end products，AGEs）存在于T细胞、单核吞噬细胞和内皮细胞上。其促炎配体S100-calgranulins在MS和相关啮齿动物模型实验性自身免疫性脑脊髓炎（EAE）中上调。当疾病由髓鞘碱性蛋白（MBP）肽或致脑炎性T细胞诱导时，或当EAE在缺乏内源性TCR和TCR链的T细胞受体（TCR）转基因小鼠中自发发生时，阻断EAE抑制EAE。抑制免疫细胞和炎性细胞对CNS的浸润明显减少。在CD 4（+）T细胞中靶向过表达显性阴性CD 4 + T细胞的转基因小鼠对MBP诱导的EAE具有抵抗性。这些数据加强了RAGE-配体相互作用在调节浸润CNS的CD 4（+）T细胞特性中的重要性。
Multiple sclerosis (MS) is a devastating neuroinflammatory disorder of the central nervous system (CNS) in which T cells that are reactive with major components of myelin sheaths have a central role. The receptor for advanced glycation end products (RAGE) is present on T cells, mononuclear phagocytes and endothelium. Its pro-inflammatory ligands, S100-calgranulins, are upregulated in MS and in the related rodent model, experimental autoimmune encephalomyelitis (EAE). Blockade of RAGE suppressed EAE when disease was induced by myelin basic protein (MBP) peptide or encephalitogenic T cells, or when EAE occurred spontaneously in T-cell receptor (TCR)-transgenic mice devoid of endogenous TCR- and TCR-chains. Inhibition of RAGE markedly decreased infiltration of the CNS by immune and inflammatory cells. Transgenic mice with targeted overexpression of dominant-negative RAGE in CD4(+) T cells were resistant to MBP-induced EAE. These data reinforce the importance of RAGE-ligand interactions in modulating properties of CD4(+) T cells that infiltrate the CNS.