Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:333

Article

Rostami, Abdolmohamad¹  Ciric, Bogoljub¹ 

[1] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA

关键词: Multiple sclerosis;    EAE;    Th1;    Th9;    Th17;    Treg;    gamma delta T cell;    IL-23;    GM-CSF;    IL-27;   

DOI  :  10.1016/j.jns.2013.03.002

来源: Elsevier

【 摘 要 】

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, Thl and Th2 cells. It was postulated that Thl cells, which produce IFN-gamma, 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 Thl cells. The Thl/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 of whether Thl 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. Thl 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/Thl paradigm. It is certain that Th17 cells will continue to be the focus of intense investigation aimed at elucidating the pathogenesis of CNS autoimmunity. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

Free