Wnt/beta-catenin 信号在协调肺泡上皮细胞与巨噬细胞宿主防御机制中的作用

项目名称： Wnt/beta-catenin 信号在协调肺泡上皮细胞与巨噬细胞宿主防御机制中的作用

项目编号： No.31472191

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 农业科学

项目作者： 刘晓明

作者单位： 宁夏大学

项目金额： 83万元

中文摘要： 肺泡作为呼吸道的终端是实现气体交换的唯一场所，无时不受到空气中微生物和异物的侵袭，是肺脏抵抗外来物的最后防线，所以，肺泡及其细胞的动态平衡是维护肺脏正常功能的关键。我们最近研究发现，Wnt/beta-catenin信号在肺泡上皮细胞（AEC）和巨噬细胞(AM)抗结核分枝杆菌BCG感染过程中发挥不尽相同的免疫调节作用，提示该信号可能在肺泡内协调肺泡上皮细胞和巨噬细胞抗感染过程中发挥作用，以维持肺泡细胞的免疫动态平衡。本项目旨在建立新型肺泡上皮细胞体外气液相培养模型的基础上，利用巨噬细胞-上皮细胞共培养技术和小鼠模型，研究肺泡内AEC和AM抗病原微生物感染的免疫学反应性，以及Wnt/?-catenin信号在协调肺泡内AEC和AM抵抗外源病原微生物感染过程中调节细胞的炎症反应性、吞噬细菌能力和细胞死亡方式的作用机制。该项目的实施对于阐明肺脏传染病的免疫致病机理有重要的理论意义。

中文关键词： 病原微生物；肺泡上皮细胞；肺泡巨噬细胞；Wnt/beta-catenin；信号；免疫调节

英文摘要： Increasing incidences of morbidity and mortality of lung diseases including the pulmonary tuberculosis and lung cancer have been reported worldwide in recent years, Alveoli of lungs are the solo sites for gas-exchanges and the terminals of the airway in lung，they are thus attacked by the exogenous microorganisms and particle materials of air, as well as the last defense line for the exogenous invasions. Therefore, the immunological homeostasis in alveoli plays a key role in normal lung function. We recently found that the Wnt/?-catenin signaling exerted different immunoregulatory functions between the alveolar epithelial cells (AEC) and alveolar macrophages (AM) in response to mycobacterial infection, which implies that it may be able to coordinate these two types of alveolar cells in response to an infection and play a regulatory role in the maintenance of immunological homeostasis in alveoli. The overall goal of present proposal is aimed to interrogate the underlying mechanisms of AECs and AMs in response to pathogenic microbial infection, and the immunoregulatory roles of Wnt/beta-catenin signaling in inflammatory responses, phagocytosis of bacteria and the modes of cell death between the AECs and AMs upon an exogenous pathogenic stimulation，using an novel air-liquid interface (ALI) AEC model, an ALI AEC/AM co-culture model and a murine model. The acomplishment of studies will provide novel insights into the underlying mechanisms of pulmonary infectious diseases.

英文关键词： pathogenic microorganism;alveolar epithelial cells;alveolar macrophages;Wnt/beta-catenin signaling;immune regulation