慢阻肺中GLP-1R信号通路介导糖代谢调控CD8+T细胞抗病毒功能的作用研究

呼吸道病毒感染是AECOPD的主要诱因，CD8+T细胞是抗病毒反应的重要免疫细胞，课题组前期研究证实COPD的CD8+T细胞呈现免疫抑制状态，同时我们发现COPD的CD8+T细胞激活后的糖代谢能力显著低于非COPD，且与糖酵解密切相关的胰高血糖素肽-1受体（GLP-1R）表达下降,GLP-1R信号通路的激活可以提高活化CD8+T细胞的糖酵解能力，逆转COPD中CD8+T细胞免疫抑制状态。据此我们推测：激活GLP-1R信号通路通过促进糖酵解途径逆转COPD中CD8+T细胞的免疫抑制状态进而增强COPD患者对抗病毒能力。我们拟通过临床、细胞、动物实验进一步探索GLP-1R信号通路在COPD的CD8+T细胞免疫过程中的作用，以及干预GLP-1R信号通路在COPD抗病毒感染中的治疗作用。该研究将丰富COPD的免疫机制研究，为防治病毒感染诱发的慢阻肺急性加重提供潜在的新的药物治疗靶点。

Respiratory virus infection is the main cause of AECOPD. The CD8+ T cell is a kind of important immune cells in the antiviral response. Our initial research and previous researches have confirmed the immune response of CD8+ T cells and the ability of using glycose in COPD patients were both lower than those in Non-COPD patients. We also found that the glucagon peptide-1 receptor (GLP-1R) expression, which was closely related to glycolysis process, was down-regulated in COPD. Activation of GLP-1R signaling could improve the glycolysis ability of activated CD8+ T cell and ameliorate their dysfunctional immunity. Based on these, we speculated that activating glp-1r signaling pathway could reverse the immunosuppressive state of CD8+T cells in COPD by promoting glycolysis pathway, thus enhancing the antivirus ability of COPD patients. We intend to further explore the role of GLP-1R signaling in the immune process of CD8+T cells of COPD and the therapeutic role of GLP-1R signaling in antiviral ability of COPD through clinical, cellular and animal experiments. This study will enrich the immune mechanism of COPD and provide a new potential therapeutic target for the prevention and treatment of acute exacerbation of COPD induced by viral infection.