FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke
FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke
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FasL-PDPK1 通路促进 CD8( ) T 细胞在缺血性中风期间的细胞毒性
DOI：
10.1007/s12975-019-00749-0
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发表时间：
2020-02-08
影响因子：
6.9
通讯作者：
Xu, Yun
中科院分区：
文献类型：
--
作者：
Fan, Lizhen;Zhang, Cun-Jin;Xu, Yun
CD8(+) T细胞被认为是缺血性卒中加重的关键因素；然而，调节CD8(+) T细胞功能的潜在机制尚未完全阐明。在这里，我们发现FasL增强了缺血性卒中后CD8(+) T细胞对神经元的细胞毒性。FasL对CD8(+) T细胞特异性失活保护脑损伤和神经元丢失。蛋白质组学分析发现，PDPK1在FasL信号的下游发挥作用，抑制PDPK1可有效降低CD8(+) T细胞的细胞毒性，改善缺血性神经功能缺损。综上所述，这些结果突出了FasL-PDPK1内在通路调节缺血性卒中中CD8(+) T细胞的细胞毒性。
CD8(+) T cells are recognized as key players in exacerbation of ischemic stroke; however, the underlying mechanism in modulating the function of CD8(+) T cells has not been completely elucidated. Here, we uncovered that FasL enhanced the cytotoxicity of CD8(+) T cells to neurons after ischemic stroke. Inactivation of FasL specific on CD8(+) T cells protected against brain damage and neuron loss. Proteomic analysis identified that PDPK1 functioned downstream of FasL signaling and inhibition of PDPK1 effectively reduced cytotoxicity of CD8(+) T cells and improved ischemic neurological deficits. Taken together, these results highlight an intrinsic FasL-PDPK1 pathway regulating the cytotoxicity of CD8(+) T cells in ischemic stroke.