LILRB4在急性肺损伤中的功能和机制研究

急性肺损伤(acute lung injury，ALI)是一种具有高死亡率的呼吸重症疾病，目前并无有效治疗手段。炎症反应过度激活是导致急性肺损伤的主要因素。以往研究显示LILRB4通过调节免疫和炎症反应在动脉粥样硬化等多种疾病中发挥重要作用，但在急性肺损伤中的功能未见报道。本项目前期研究发现，在LPS诱导的急性肺损伤小鼠肺组织中，LILRB4的mRNA和蛋白表达均显著上升，且集中在巨噬细胞中。因此，我们推断LILRB4可能通过调节巨噬细胞炎症反应调控急性肺损伤。本项目拟通过应用LILRB4基因敲除小鼠建立LPS诱导的急性肺损伤模型，评价LILRB4在急性肺损伤中的作用。并通过体外原代巨噬细胞阐明LILRB4在调控巨噬细胞炎症反应的功能，最后再应用转录组学和互作蛋白组学联合分析寻找LILRB4调控急性肺损伤的分子机制，为寻找防治急性肺损伤的药物靶点提供重要的理论基础。

Acute lung injury (ALI) is a severe respiratory disease with high mortality but no effective treatment currently. Excessive activation of inflammatory responses is a major cause of development of ALI. Previous studies have shown that LILRB4 plays an important role in many diseases such as atherosclerosis by regulating immune and inflammatory responses, but the function of LILRB4 in ALI has not been reported. In the preliminary study, we have found that LILRB4 mRNA and protein expression were significantly increased in LPS-induced lung tissues of mice, which mainly located in macrophages. Therefore, we hypothesize that LILRB4 may regulate the pathogenesis of ALI by modulating macrophage inflammatory response. In this study, we intend to determine the exact function of LILRB4 in the pathogenesis of ALI by establishing LPS-induced ALI model in LILRB4 knockout mice. Then we will isolate primary macrophages and evaluate the effect of LILRB4 on the inflammatory response in vitro. Finally, using RNA-Seq and interaction proteomics, we will elucidate the mechanism by which LILRB4 regulates the function of macrophage and ALI. This work will provide theory evidence for searching for the novel therapeutic targets of ALI.