慢阻肺存在调节性T细胞（Treg）数量与功能紊乱，机制不详。M4型毒蕈碱受体（M4R）不但分布于脑部各区域，而且在淋巴细胞上也有表达，通过Gi/o信号通路发挥抑炎作用。我们首次发表的成果指出：Treg主要表达M4R，Th1/Th17低表达M4R；COPD患者M4R/M5R比例较正常人表达降低。预实验表明，激动M4R受体能协同TGF-β促进Treg的分化。鉴此，我们推测M4R表达变化可以导致Treg的诱导分化异常，是COPD发病的重要机制之一。为此，我们将研究COPD外周血CD4+T细胞的M4R表达，并采用香烟提取物、M4R激动剂/抑制剂或基因过表达/干扰、信号分子拮抗剂等技术，研究M4R对Treg增殖凋亡、诱导分化和抑制功能的影响，揭示M4R和Treg的内在关系和信号通路，为防治COPD提供新靶点。

Abnormal regulatory T cells (Treg) in number and function have been described in COPD, but the underlying mechanism remains unclear. Muscarinic M4 receptors (M4R) are not only expressed in brain regions, but also in lymphocytes, and play a role in suppressing inflammation through Gi/o signaling pathway. Our previously published results showed for the first time that MR4 mRNA was increased in Treg while decreased in Th1/Th17; and the relative expression of M4R/M5R in COPD was lower than that in healthy subjects. In addition, the preliminary experiments showed that activation of M4R potentiated the differentiation of Treg when combined with TGF-β. To verify this hypothesis, we will detect the expression of M4R in peripheral blood CD4+T cells of COPD patients. Additionally, to certify the effect of M4R on proliferation/apoptosis/differentiation/suppression function of Treg, we will take advantage of M4R agonists/inhibitors, overexpression/interference of genes and signal antagonists. The future project will reveal the inherent relationship and signaling pathways between Treg and M4R, and finally provide a new target for the prevention and treatment of COPD.