Takarada-Iemata Mika, Hori Osamu
Department of Neuroanatomy, Kanazawa University Graduate School of Medical Sciences.
Nihon Yakurigaku Zasshi. 2021;156(4):230-234. doi: 10.1254/fpj.21030.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), and is designated as an intractable disease in Japan. It is characterized by dissemination of plaque-like sclerosis in space and time, accompanied with various symptoms corresponding to the CNS lesion site. Typically, neurological symptoms chronically progress accompanied with relapses and remissions, and there is still no curative therapy. A number of studies using MS specimen and the animal MS model experimental autoimmune encephalomyelitis (EAE) have shown that MS is an autoimmune disease that targets myelin sheath in the CNS. Autoreactive T cells and B cells play a central role in pathogenesis of MS. MS comprise relapsing-remitting MS and progressive MS, the latter accumulates clinical disability without relapse. Based on the importance of adaptive immunity, various disease-modifying drugs have been developed to treat relapsing-remitting MS. On the other hand, an effective treatment for progressive MS has not yet been established. Increasing evidence have been recognized glial cells as key components of MS immunopathology, in addition to innate immunity and adaptive immunity. However, molecular mechanisms of crosstalk between immune cells, glial cells and neurons remain to be elucidated. Here, we review MS pathology and recent advances in the disease-modifying therapy that efficiently reduce disease activity in relapsing-remitting MS and introduce an update of recent evidence that astrocyte is involved in the MS pathology with including our research analyzed in mouse EAE model.
多发性硬化症(MS)是一种中枢神经系统(CNS)的炎性脱髓鞘疾病,在日本被指定为难治性疾病。其特征是斑块状硬化在空间和时间上的播散,并伴有与CNS病变部位相对应的各种症状。通常,神经症状会随着复发和缓解而慢性进展,并且仍然没有治愈性疗法。许多使用MS标本和动物MS模型实验性自身免疫性脑脊髓炎(EAE)的研究表明,MS是一种针对CNS中髓鞘的自身免疫性疾病。自身反应性T细胞和B细胞在MS的发病机制中起核心作用。MS包括复发缓解型MS和进展型MS,后者在无复发的情况下累积临床残疾。基于适应性免疫的重要性,已经开发了各种疾病修饰药物来治疗复发缓解型MS。另一方面,尚未确立针对进展型MS的有效治疗方法。除了固有免疫和适应性免疫外,越来越多的证据表明神经胶质细胞是MS免疫病理学的关键组成部分。然而,免疫细胞、神经胶质细胞和神经元之间相互作用的分子机制仍有待阐明。在此,我们综述了MS病理学以及在复发缓解型MS中有效降低疾病活动的疾病修饰疗法的最新进展,并介绍了最近有关星形胶质细胞参与MS病理学的证据更新,包括我们在小鼠EAE模型中分析的研究。