Double-negative T cells remarkably promote neuroinflammation after ischemic stroke
Double-negative T cells remarkably promote neuroinflammation after ischemic stroke
复制标题
双阴性T细胞显着促进缺血性中风后的神经炎症
DOI：
10.1073/pnas.1814394116
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发表时间：
2019-03-19
影响因子：
11.1
通讯作者：
Xu, Yun
中科院分区：
文献类型：
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作者：
Meng, Hailan;Zhao, Haoran;Xu, Yun
CD 3（+）CD 4（-）CD 8（-）T细胞（双阴性T细胞; DNT）通过调节免疫和炎症稳态在外周免疫相关疾病中具有多种功能。然而，DNT在中枢神经系统中的功能仍然未知。在这里，我们发现DNT的水平在中风患者的大脑和外周血中以及在小鼠模型中以时间依赖性的方式显著增加。浸润的DNT通过调节FasL/PTPN 2/TNF-α信号通路增强脑免疫和炎症反应，加重缺血性脑损伤。阻断该通路可限制DNT介导的神经炎症，改善卒中的结局。我们的研究结果确定了DNT在缺血性脑中的关键功能，表明这一独特的人群是治疗缺血性卒中的一个有吸引力的靶点。
CD3(+)CD4(-)CD8(-) T cells (double-negative T cells; DNTs) have diverse functions in peripheral immune-related diseases by regulating immunological and inflammatory homeostasis. However, the functions of DNTs in the central nervous system remain unknown. Here, we found that the levels of DNTs were dramatically increased in both the brain and peripheral blood of stroke patients and in a mouse model in a time-dependent manner. The infiltrating DNTs enhanced cerebral immune and inflammatory responses and exacerbated ischemic brain injury by modulating the FasL/PTPN2/TNF-alpha signaling pathway. Blockade of this pathway limited DNT-mediated neuroinflammation and improved the outcomes of stroke. Our results identified a critical function of DNTs in the ischemic brain, suggesting that this unique population serves as an attractive target for the treatment of ischemic stroke.