当前位置: X-MOL 学术Neurochem. Int. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Eomes-expressing T-helper cells as potential target of therapy in chronic neuroinflammation.
Neurochemistry international ( IF 4.4 ) Pub Date : 2018-12-01 , DOI: 10.1016/j.neuint.2018.11.023
Shinji Oki 1
Affiliation  

Reserch progresses in understanding the pathogenicity of multiple sclerosis (MS) in the last couple of decade has enabled us to develop new drug entities available in the clinic. However, we still have not succeeded in preventing conversion from relapsing-remitting MS (RR-MS) to secondary progressive MS (SP-MS) and curing this intractable form of MS. Furthermore, diagnosis is usually retrospective and subjective, relying on gradual worsening of neurological signs/symptoms. This is obviously due to the lack of understanding for the pathogenicity driving disease progression in MS and of reliable biomarkers reflecting the progressive or stationary disease status. Two relevant components are involved in brain pathology of SP-MS, neurodegeneration and inflammation. Neurodegeneration may occur spontaneously in a neuron-intrinsic manner under chronic inflammation, such as glutamate excitotoxicity, mitochondrial/oxidative injury with iron deposit in the brain, and loss of trophic support. Meanwhile, inflammation is usually associated with recurrent relapse and the cumulative infiltration of immune cells, including T cells, B cells, and myeloid cells of peripheral or CNS origin, could ignite the processes of neurodegeneration. Especially, the higher frequency of leptomeningeal follicle-like structures observed in SP-MS patients suggests that immune cells sheltered behind a blood-brain barrier is still active under smoldering CNS inflammation. Recent successes in Ocrelizumab for primary progressive in MS (PP-MS) and Siponimod for SP-MS reappraised the importance of immune cells for pathogenesis progressive MS. Accordingly, our recent comparative analysis between MS and its animal model, experimental autoimmune encephalomyelitis (EAE), raises a new possibility that ectopic expression of eomesodermin (Eomes) in helper T (Th) cells constitutes a previously unappreciated subset of Th cells with cytotoxic potential against neuronal cells. In this review article, I will summarize the mechanisms proposed on pathogenesis of SP-MS and propose a new pathogenic mechanism for neurodegeneration mediated by unique cytotoxic Th cells.

中文翻译:

表达Eomes的T辅助细胞是慢性神经炎症治疗的潜在目标。

在过去的十年中,研究人员在了解多发性硬化症(MS)的致病性方面取得了进步,这使我们能够开发出可在临床上使用的新药物。但是,我们仍然未能成功阻止从复发缓解型MS(RR-MS)转化为继发进行性MS(SP-MS)并治愈这种难治性的MS。此外,诊断通常是回顾性和主观性的,取决于神经系统体征/症状的逐渐恶化。显然,这是由于缺乏对MS致病性驱动疾病进展的认识,以及对反映疾病进展或静止状态的可靠生物标志物的了解。SP-MS的脑病理学涉及两个相关成分,即神经变性和炎症。在慢性炎症(例如谷氨酸兴奋性中毒,线粒体/氧化性损伤以及脑中铁沉积以及营养支持的丧失)下,神经退行性变可能以神经元内在的方式自发发生。同时,炎症通常与复发复发有关,并且外周或CNS起源的免疫细胞(包括T细胞,B细胞和髓样细胞)的累积浸润可以点燃神经变性的过程。特别是,在SP-MS患者中观察到的较高的软脑膜滤泡样结构频率表明,在阴燃的CNS炎症下,躲在血脑屏障后面的免疫细胞仍处于活动状态。Ocrelizumab用于原发性进展型MS(PP-MS)和Siponimod用于SP-MS的近期成功重新评估了免疫细胞在发病机理中进展性MS的重要性。因此,我们最近在MS及其动物模型实验性自身免疫性脑脊髓炎(EAE)之间进行的比较分析提出了新的可能性,即Eomesodermin(Eomes)在辅助性T(Th)细胞中异位表达构成了以前未被认识的具有细胞毒性潜能的Th细胞亚群。针对神经细胞。在这篇综述文章中,我将总结有关SP-MS发病机理的机制,并提出由独特的细胞毒性Th细胞介导的神经退行性疾病的新发病机制。
更新日期:2018-12-01
down
wechat
bug