白血病抑制因子
神经保护
CD8型
免疫学
细胞毒性T细胞
炎症
医学
生物
神经科学
免疫系统
白细胞介素6
生物化学
体外
作者
Wei Cai,Ligen Shi,Jingyan Zhao,Fei Xu,Connor Dufort,Qing Ye,Tuo Yang,Xuejiao Dai,Junxuan Lyu,Cheng‐Hao Jin,Hongjian Pu,Fang Yu,Sulaiman H Hassan,Zeyu Sun,Wenting Zhang,T. Kevin Hitchens,Yejie Shi,Angus W. Thomson,Rehana K. Leak,Xiaoming Hu,Jun Chen
摘要
Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms. We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection. TRL depletion worsened stroke outcomes, an effect reversed by CD8+ TRL reconstitution. The CXCR3/CXCL10 axis served as the brain-homing mechanism for CD8+ TRLs. Upon brain entry, CD8+ TRLs were reprogrammed to upregulate leukemia inhibitory factor (LIF) receptor, epidermal growth factor-like transforming growth factor (ETGF), and interleukin 10 (IL-10). LIF/LIF receptor interactions induced ETGF and IL-10 production in CD8+ TRLs. While IL-10 induction was important for the antiinflammatory effects of CD8+ TRLs, ETGF provided direct neuroprotection. Poststroke intravenous transfer of CD8+ TRLs reduced infarction, promoting long-term neurological recovery in young males or aged mice of both sexes. Thus, these unique CD8+ TRLs serve as early responders to rally defenses against stroke, offering fresh perspectives for clinical translation.
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