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

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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