本团队前期研究发现大环内酯类抗生素抑制了烟雾诱导的小鼠气道中性粒细胞炎症，且有研究表明不同炎症表型哮喘患者气道微生态存在差异，提示微生态与气道炎症及局部免疫相关。我们还发现，大肠杆菌脂多糖诱导气道上皮细胞高表达EDCs，后者可活化ILC2产生2型细胞因子，提示了在哮喘发病中上皮细胞通过EDCs连接了固有免疫和适应性免疫。研究表明ILCs不表达PRRs，无法直接识别微生物，因而我们推测微生态可能间接通过活化气道上皮细胞调控ILC亚群。本项目通过比较无菌和带菌条件下OVA炎症小鼠气道EDCs的表达、ILC亚群分化及功能的差异，并采用经滴鼻接种肺泡灌洗液、经灌胃接种粪便的方法进行微生态过继，应用各EDCs的中和性抗体、TLR4-/-小鼠等工具研究微生态调控ILC亚群的具体机制。本项目的完成将进一步阐明气道粘膜固有免疫参与哮喘发病的机制，为激素治疗效果欠佳的哮喘患者提供更多可能的治疗靶点。

We previously found that macrolides antibiotics attenuated cigarette smoking-induced neutrophilic airway inflammation and, as is documented, airway microbiota differs among different inflammatory phenotypes in asthma patients, suggesting a relationship exist among microbiota, airway inflammation, and local immunity. We also discovered, in epithelial cells, escherichia coli-derived LPS elevated EDCs production, which is known to activate ILC2 to generate type 2 cytokines, bridging innate immunity and adaptive immunity in asthma. Expression of PRRs on ILCs has not been reported. Therefore, we propose a hypothesis that microbiota regulates ILC subsets through activation of airway epithelial cells. This program adopted GF mice, transferred BALF or stool from asthma patients or OVA-treated conventional mice to GF mice so as to identify the roles of microbiota at different sites in innate immune response and adopted neutralizing antibodies (to EDCs) and TLR4-/- mice to elucidate the mechanism of epithelial cells in bridging microbiota and ILC subsets. This project will clarify the mechanism of airway mucosal immunity in the pathogenesis of asthma and provide a new target for the treatment of steroid-resistant asthma.