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

Lizhen Fan, Cun-Jin Zhang, Liwen Zhu, Jian Chen, Zhi Zhang, Pinyi Liu, Xiang Cao, Hailan Meng, Yun Xu

Translational stroke research 2020 Aug

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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.

Citation

Lizhen Fan, Cun-Jin Zhang, Liwen Zhu, Jian Chen, Zhi Zhang, Pinyi Liu, Xiang Cao, Hailan Meng, Yun Xu. FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke. Translational stroke research. 2020 Aug;11(4):747-761