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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We thank Translational Medicine Core facilities in Medical School of Nanjing University for proteomic analysis. We thank Yan Zhang, Yue Gu, and Xinyu Bao for their technical support.
This research was supported by the National Natural Science Foundation of China (81230026, 81630028, 81701235, 81701168), the Science and Technology Department of Jiangsu Province (BE2016610), and the Jiangsu Province Key Medical Discipline (ZDXKA2016020).
Conflict of Interest
All authors read and approved the final manuscript. The authors declare no conflict of interest.
This study was carried out in accordance with the recommendations of institutional guidelines and approved by the Animal Care Committee in Nanjing University.
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Fan, L., Zhang, C., Zhu, L. et al. FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke. Transl. Stroke Res. (2020). https://doi.org/10.1007/s12975-019-00749-0
- CD8+ T cells