颗粒酶B
星形胶质细胞
穿孔素
血脑屏障
CCL5
神经炎症
颗粒酶
CD8型
生物
封堵器
免疫系统
细胞生物学
癌症研究
免疫学
化学
炎症
T细胞
紧密连接
白细胞介素2受体
神经科学
中枢神经系统
作者
Shiyi Zhou,Chang Liu,Jixian Wang,Jing Ye,Qianyuan Lian,Lin Gan,Shiyu Deng,Tongtong Xu,Yiyan Guo,Wanlu Li,Zhijun Zhang,Guo‐Yuan Yang,Yaohui Tang
标识
DOI:10.1177/0271678x231214838
摘要
The crosstalk between reactive astrocytes and infiltrated immune cells plays a critical role in maintaining blood-brain barrier (BBB) integrity. However, how astrocytes interact with immune cells and the effect of their interaction on BBB integrity after hemorrhagic stroke are still unclear. By performing RNA sequencing in astrocytes that were activated by interleukin-1α (IL-1α), tumor necrosis factor α (TNFα), and complement component 1q (C1q) treatment, we found CCL5 was among the top upregulated genes. Immunostaining and western blot results demonstrated that CCL5 was increased in mice brain after hemorrhagic stroke. Flow cytometry showed that knockout of astrocytic CCL5 reduced the infiltration of CD8+ but not CD4+ T and myeloid cells into the brain (p < 0.05). In addition, knockout CCL5 in astrocytes increased tight junction-related proteins ZO-1 and Occludin expression; reduced Evans blue leakage, perforin and granzyme B expression; improved neurobehavioral outcomes in hemorrhagic stroke mice (p < 0.05), while transplantation of CD8+ T cells reversed these protective effects. Moreover, co-culture of CD8+ T cells with bEnd.3 cells induced the apoptosis of bEnd.3 cells, which was rescued by inhibiting perforin. In conclusion, our study suggests that CCL5 mediated crosstalk between astrocytes and CD8+ T cells represents an important therapeutic target for protecting BBB in stroke.
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