气道重塑是导致重症哮喘患者死亡的主要原因之一。肺巨噬细胞向M2型极化，致气道上皮下纤维化是哮喘气道重塑主要机制之一，寻找巨噬细胞向M2型极化的启动机制和早期阻断办法，是目前哮喘研究的热点。我们前期研究证实溶血磷脂酰胆碱（lysoPC）是参加哮喘气道炎症和气道高反应性的关键物质，但其对哮喘气道重塑的作用尚不明确。我们预实验发现，lysoPC调节小鼠肺巨噬细胞向M2型极化，具体机制尚不明确，可能与其受体及下游信号STAT6、IRF4有关，推测lysoPC可能通过调节肺巨噬细胞M2型极化参与哮喘气道重塑。本项目拟以基因敲除的巨噬细胞和哮喘小鼠为研究对象，从体内和体外探索lysoPC调节肺巨噬细胞M2型极化，参与哮喘气道重塑的可能机制和相关信号途径，为进一步阐明哮喘气道重塑的机制和寻找新的治疗靶点提供实验依据。

Airway remodeling is a major cause of death among patients with severe asthma. It is well recognized that M2 polarization of lung macrophages leads to subepithelial fibrosis, which is a crucial component of airway remodeling in asthma. Recently, lots of studies have been undertaken to investigate the molecular mechanisms underlying the initiation and inhibition of M2 polarization. Our previous research has demonstrated that lysophosphatidylcholine (lysoPC) played a critical role in asthma airway inflammation and hyperreactivity for the first time, but its role in airway remodeling is unknown. In the preliminary experiment, we found lysoPC could regulate the mice lung macrophages polarization to M2 type. Moreover, its receptor and downstream signal including STAT6 and IRF4 were involved in M2 polarization. We hypothesized that lysoPC might participate in the airway remodeling through regulating the lung macrophages polarization to M2 type in asthma. By using gene knock-out macrophages and a mouse model of asthma, we plan to investigate the capacity and molecular mechanism by which lysoPC regulates lung macrophages polarization in the development of airway remodeling. Clarification of the role of lysoPC in asthma will potentially improve the prevention and management of the disease.