Journal
TRANSLATIONAL STROKE RESEARCH
Volume 11, Issue 4, Pages 747-761Publisher
SPRINGER
DOI: 10.1007/s12975-019-00749-0
Keywords
stroke; FasL; CD8(+) T cells; neurons; PDPK1; cytotoxicity
Categories
Funding
- National Natural Science Foundation of China [81230026, 81630028, 81701235, 81701168]
- Science and Technology Department of Jiangsu Province [BE2016610]
- Jiangsu Province Key Medical Discipline [ZDXKA2016020]
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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.
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