Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination.
Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination.
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DOI：
10.1016/j.jns.2013.03.002
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发表时间：
2013-10-15
影响因子：
4.4
通讯作者：
Ciric, Bogoljub
中科院分区：
文献类型：
--
作者：
Rostami, Abdolmohamad;Ciric, Bogoljub
多发性硬化（MS）是中枢神经系统（CNS）的自身免疫性疾病。MS的病因学尚未完全了解，但据信髓鞘特异性CD 4 + T细胞在引发和协调CNS炎症中发挥核心作用。在这种情况下，在外周活化的CD 4 + T细胞浸润CNS，在那里，通过分泌细胞因子和趋化因子，它们开始炎症级联反应。由于CD 4 + T细胞在CNS自身免疫中的核心作用，它们已被广泛研究，主要是通过使用实验性自身免疫性脑脊髓炎（EAE），MS的动物模型。在20世纪80年代后期，CD 4 + T细胞，基于它们的细胞因子产生，被分为两个辅助谱系，Th 1和Th 2细胞。据推测，产生IFN-γ的Th 1细胞介导MS/EAE中CNS的炎症，而产生IL-4的Th 2细胞由于其对Th 1细胞的拮抗作用而在疾病中具有有益作用。Th 1/Th 2模式仍然是MS/EAE发病机制的主流观点，直到2005年发现了一个新的谱系，Th 17。在相对较短的时间内，Th 17细胞（以其标志性细胞因子IL-17 A命名）在许多炎症性疾病（包括EAE）中起着至关重要的作用，并且可能在MS中也起着重要作用。Th 17范式发展迅速，引发了关于Th 1细胞是否参与EAE/MS发病机制的争论，或者它们是否甚至可能由于其对Th 17细胞的拮抗作用而具有保护作用。许多研究结果支持Th 17细胞在自身免疫性CNS炎症中发挥重要作用的观点，可能主要是在疾病的初始阶段。Th 1细胞可能有助于发病机制，其作用可能在疾病后期更加明显。因此，目前关于Th细胞在MS/EAE发病机制中的作用的观点可称为Th 17/Th 1范式。可以肯定的是，Th 17细胞将继续成为旨在阐明CNS自身免疫发病机制的深入研究的焦点。
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). The etiology of MS is not well understood, but it is believed that myelin-specific CD4+ T cells play a central role in initiating and orchestrating CNS inflammation. In this scenario, CD4+ T cells, activated in the periphery, infiltrate the CNS, where, by secreting cytokines and chemokines, they start an inflammatory cascade. Given the central role of CD4+ T cells in CNS autoimmunity, they have been studied extensively, principally by using experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the late 1980s, CD4+ T cells, based on their cytokine production, were divided into two helper lineages, Th1 and Th2 cells. It was postulated that Th1 cells, which produce IFN-γ, mediate inflammation of the CNS in MS/EAE, while Th2 cells, which produce IL-4, have a beneficial effect in disease, because of their antagonistic effect on Th1 cells. The Th1/Th2 paradigm remained the prevailing view of MS/EAE pathogenesis until 2005, when a new lineage, Th17, was discovered. In a relatively short period of time it became apparent that Th17 cells, named after their hallmark cytokine, IL-17A, play a crucial role in many inflammatory diseases, including EAE, and likely in MS as well. The Th17 paradigm developed rapidly, initiating the debate whether Th1 cells contribute to EAE/MS pathogenesis at all, or if they might even have a protective role due to their antagonistic effects on Th17 cells. Numerous findings support the view that Th17 cells play an essential role in autoimmune CNS inflammation, perhaps mainly in the initial phases of disease. Th1 cells likely contribute to pathogenesis, with their role possibly more pronounced later in disease. Hence, the current view on the role of Th cells in MS/EAE pathogenesis can be called the Th17/Th1 paradigm. It is certain that Th17 cells will continue to be the focus of intense investigation aimed at elucidating the pathogenesis of CNS autoimmunity.
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影响因子：
15.3
作者：
Bettelli, E;Sullivan, B;Szabo, SJ;Sobel, RA;Glimcher, H;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1152/ajplung.00275.2003
发表时间：
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影响因子：
4.9
作者：
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影响因子：
15.9
作者：
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
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