β-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration
β-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration
复制标题
DOI：
10.1038/s41586-019-0964-2
复制
发表时间：
2019-02-28
期刊：
影响因子：
64.8
通讯作者：
Fluegel, Alexander
中科院分区：
文献类型：
--
作者：
Lodygin, Dmitri;Hermann, Moritz;Fluegel, Alexander
灰质是神经退行性疾病如帕金森病和阿尔茨海默病的病理过程的中心目标。多发性硬化症是一种中枢神经系统的自身免疫性疾病，灰质也经常受到影响。多发性硬化症中灰质炎症和变性的机制尚不清楚。在这里，我们表明，在刘易斯大鼠，针对神经元蛋白β-突触核蛋白的T细胞特异性侵入灰质，这是伴随着多方面的临床疾病的介绍。β-突触核蛋白的表达模式诱导这些T细胞的局部活化，并因此确定组织的炎症引发和免疫细胞的靶向募集。由此产生的炎症导致了灰质的显著变化，从神经胶质增生和神经元破坏到脑萎缩。在人类中，β-突触核蛋白特异性T细胞在慢性进展性多发性硬化症患者中富集。这些发现揭示了β-突触核蛋白在引起T细胞介导的中枢神经系统病理学中的先前未被认识的作用。
The grey matter is a central target of pathological processes in neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. The grey matter is often also affected in multiple sclerosis, an autoimmune disease of the central nervous system. The mechanisms that underlie grey matter inflammation and degeneration in multiple sclerosis are not well understood. Here we show that, in Lewis rats, T cells directed against the neuronal protein beta-synuclein specifically invade the grey matter and that this is accompanied by the presentation of multifaceted clinical disease. The expression pattern of beta-synuclein induces the local activation of these T cells and, therefore, determined inflammatory priming of the tissue and targeted recruitment of immune cells. The resulting inflammation led to significant changes in the grey matter, which ranged from gliosis and neuronal destruction to brain atrophy. In humans, beta-synuclein-specific T cells were enriched in patients with chronic-progressive multiple sclerosis. These findings reveal a previously unrecognized role of beta-synuclein in provoking T-cell-mediated pathology of the central nervous system.