CD40 对烟草烟雾暴露下小鼠树突状细胞诱导Th17分化的调控作用研究

烟草烟雾暴露是COPD (chronic obstructive pulmonary diseases)炎症最重要的危险因素，Th17是COPD慢性炎症的主要效应细胞，而树突状细胞在抗原递呈诱导T细胞的分化中起关键作用。我们的前期研究提示香烟提取物刺激可以促进树突状细胞上调CD40表达。CD40是树突状细胞表面的共刺激分子，研究显示在感染状态下树突状细胞可通过CD40/CD40L途径促进CD4+T细胞向Th17分化。据此，我们推测在烟草烟雾暴露下，CD40可能是树突细胞促进CD4+T细胞向Th17分化的重要的调控因子。故本项目以CD40为靶点，首先观察烟草烟雾暴露下CD40敲除小鼠树突状细胞的功能状态和Th17变化，进而研究在阻断CD40/CD40L路径条件下树突细胞对CD4+T细胞向Th17的分化的影响，为COPD的防治提供新的思路及靶点。

Cigarette smoking is the most important risk factor for chronic obstructive pulmonary disease(COPD). Th17 engages on the chronic inflammation of COPD,while dendritic cells play an vital role in the differentiation of T cells.In our previous studies, we found that the expression of CD40 on dendritic cells was upregulated after challenged by cigarette smoke extract(CSE) .CD40 is a costimulatory molecule on the surface of dendritic cell and there are studies reported that dendritic cells can promote CD4+T cells differentiate into Th17 cell by CD40/CD40L pathway under infection status.Thus, we speculated that CD40 may be an essential regulatory molecule of dendritic cell in the promotion of CD4+T cell differentiated into Th17 under the circumstance of cigarette smoke exposure.In present study, We first observe the function changes of dendritic cell and Th17 cell in CD40 knockout mice aftercigarette smoke exposure.Subsequently, we investigate the effect of blocking the CD40/CD40L pathway on the differentiation of Th17 induced by dendritic cell and aim to provide a noval target for the prevention and treatment of COPD.