FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke

被引：44

作者：

Fan, Lizhen ^{[1
,2
,3
]}

Zhang, Cun-Jin ^{[1
,2
,3
]}

Zhu, Liwen ^{[1
,2
,3
]}

Chen, Jian ^{[1
,2
,3
]}

Zhang, Zhi ^{[1
,2
,3
]}

Liu, Pinyi ^{[1
,2
,3
]}

Cao, Xiang ^{[1
,2
,3
]}

Meng, Hailan ^{[1
,2
,3
]}

Xu, Yun ^{[1
,2
,3
,4
,5
]}

机构：

[1] Nanjing Univ, Sch Med, Drum Tower Hosp, Dept Neurol, Nanjing 210008, Peoples R China

[2] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210008, Peoples R China

[3] Nanjing Univ, Jiangsu Key Lab Mol Med, Sch Med, Nanjing 210008, Peoples R China

[4] Jiangsu Prov Stroke Ctr Diag & Therapy, Nanjing 210008, Peoples R China

[5] Nanjing Neuropsychiat Clin Med Ctr, Nanjing 210008, Peoples R China

来源：

TRANSLATIONAL STROKE RESEARCH | 2020年 / 11卷 / 04期

基金：

中国国家自然科学基金;

关键词：

stroke; FasL; CD8(+) T cells; neurons; PDPK1; cytotoxicity; PROTEIN-KINASE; EXPRESSION; BRAIN; PDK1; LYMPHOCYTES; SUPPRESSES; GLYCOLYSIS; MIGRATION; APOPTOSIS; ROLES;

D O I：

10.1007/s12975-019-00749-0

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：747 / 761

页数：15

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