Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210008, China; Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.
Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210008, China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.
Neurosci Lett. 2022 Apr 17;776:136563. doi: 10.1016/j.neulet.2022.136563. Epub 2022 Feb 28.
γδ T cells were reported to play a key role in ischemic stroke. The integrity of the blood-brain barrier (BBB) directly affects the prognosis of ischemic stroke. This study aimed to determine whether γδ T cells aggravate BBB injury and determine the outcome of ischemic stroke.
Oxygen-glucosedeprivation (OGD) and middle cerebral artery occlusion (MCAO) were used as ischemic stroke models in vitro and in vivo. Flow cytometry was used to evaluate the intracranial infiltration of γδ T cells. RT-qPCR was used to evaluatethe mRNA levels of cytokines and γδ T cell markers. ELISA was used to test the levels of cytokines. Immunofluorescence, TEER and western blotting were used to measure BBB injury.
In this study, we found that a large number of γδ T cells infiltrated the ischemic penumbra 24 h after MCAO. Knockout of γδ T cells improved the motor function injury induced by MCAO and significantly reduced the volume of cerebral infarction and blood-brain barrier injury. IL-17A neutralization could rescue the BBB injury induced by γδ T cells both in vitro and in vivo.
Peripheral γδ T cells immediately infiltrated into the lesion site after ischemic stroke and aggravated BBB injury by releasing IL-17A, which might be a potential therapeutic target for ischemic stroke.
γδ T 细胞被报道在缺血性中风中发挥关键作用。血脑屏障（BBB）的完整性直接影响缺血性中风的预后。本研究旨在确定 γδ T 细胞是否加重 BBB 损伤，并确定缺血性中风的结局。
氧葡萄糖剥夺（OGD）和大脑中动脉闭塞（MCAO）分别用于体外和体内缺血性中风模型。流式细胞术用于评估颅内 γδ T 细胞浸润。RT-qPCR 用于评估细胞因子和 γδ T 细胞标志物的 mRNA 水平。ELISA 用于检测细胞因子水平。免疫荧光、TEER 和 Western blot 用于测量 BBB 损伤。
在本研究中，我们发现 MCAO 后 24 小时，大量 γδ T 细胞浸润到缺血半影区。敲除 γδ T 细胞可改善 MCAO 引起的运动功能损伤，并显著降低脑梗死体积和 BBB 损伤。IL-17A 中和在体外和体内均可挽救 γδ T 细胞引起的 BBB 损伤。
缺血性中风后，外周 γδ T 细胞立即浸润到病变部位，并通过释放 IL-17A 加重 BBB 损伤，这可能是缺血性中风的潜在治疗靶点。
