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

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Abstract

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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Acknowledgments

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.

Funding

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).

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Author notes

  1. Lizhen Fan and Cun-Jin Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210008, China

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

  2. Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, 210008, China

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

  3. Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, 210008, China

    Yun Xu

  4. Nanjing Neuropsychiatry Clinic Medical Center, Nanjing, 210008, China

    Yun Xu

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  1. Lizhen Fan
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Contributions

Yun Xu designed and coordinated the study, analyzed the data, and revised the paper. Lizhen Fan and Cunjin Zhang performed the experiments, wrote the manuscript, and revised the figures. Liwen Zhu, Jian Chen, Xiang Cao, Pinyi Liu, Zhi Zhang, and Hailan Meng helped with the experiments. Lizhen Fan and Cun-Jin Zhang contributed equally to this work.

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Correspondence to Yun Xu.

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All authors read and approved the final manuscript. The authors declare no conflict of interest.

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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, CJ., Zhu, L. et al. FasL-PDPK1 Pathway Promotes the Cytotoxicity of CD8+ T Cells During Ischemic Stroke. Transl. Stroke Res. 11, 747–761 (2020). https://doi.org/10.1007/s12975-019-00749-0

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