拟杆菌和梭菌在DEE暴露致气道重塑中的作用及胞外囊泡（EVs）的调控机制研究

柴油机尾气（Diesel engine exhaust，DEE）成为世界范围内危害公共卫生的最大威胁之一，呼吸道成为其损害的首要靶器官，然而针对呼吸道损害的分子机制尚未明确。DEE深入肺脏并改变肺部微环境，进而影响肺部菌群的定植。肺部菌群能够影响呼吸道免疫反应，呼吸道炎症反应往往伴随气道重塑。细菌借助胞外囊泡(Extracellular vesicles, EVs)将自身物质传递给远端的免疫细胞，调节宿主的免疫反应。前期研究发现DEE暴露人群的气道重塑相关指标与肺部菌群丰度均出现显著差异。因此我们提出科学假设：DEE暴露引起肺部菌群失衡，产生的EVs穿过呼吸道粘膜引发肺部免疫反应，通过肺部菌群-EVs-免疫反应途径导致暴露人群的气道重塑。本课题的研究将拓展DEE暴露致气道重塑调控机制的认识，为阐明肺部菌群紊乱与气道重塑的关系提供科学依据，为精准预防DEE引起的气道重塑提供理论依据。

Diesel engine exhaust (DEE) has become one of the major threats to the public health in the world, which primarily endangers the organ of airway. However, the detailed mechanism of specific toxicity to airway remains unclear. DEE is proved to penetrate the depth of lung, change the lung microenvironment and influence the colonization of lung microbiome. Lung microbiome is reported to regulate the immune response in lung, which is usually accompanied by airway remodeling. Bacteria mostly delivers its molecules to distal host cells in virtue of extracellular vesicles (EVs) to modulate the immune response of host. Our preliminary data indicate the obvious alter of parameters of airway modeling and the abundance of Bacteroidales and Clostridiales in lung. On the basis, we hypothesize that DEE exposure affects the airway remodeling through the pathway of lung microbiome-EVs-airway epithelial cells-immune response. The project will expand our awareness of the mechanism modulating airway remodeling when exposed to DEE, provide important scientific basis for explaining the relation between dysbiosis of lung microbiome and airway remodeling, and furnish theoretical guidance for precise prevention against airway remodeling induced by DEE exposure.