嗜酸粒细胞性支气管炎(EB)为我国慢性咳嗽最常见的病因之一，患病率明显高于欧美。EB大多缺乏变应征，气道嗜酸细胞增高并非主要由Th2通路所致，但病因未明。柴油车尾气颗粒（DEPs）是我国城市大气PM2.5重要来源，可引起咳嗽及实验动物非变应性嗜酸细胞气道炎症。由于嗜酸祖细胞（EoP）原位分化可导致局部嗜酸细胞炎症，我们推测：DEPs可以损伤上皮激活ILC2引起EOP原位分化，导致局部非变应性嗜酸细胞性炎症的产生。本项目将观察不同表型EB患者EoP原位分化水平及其与ILC2的关系；构建支气管上皮细胞与ILC2共培养体系，结合柴油车尾气暴露小鼠实验，从细胞及动物实验水平上探讨DEPs通过激活ILC2介导的EoP原位分化的作用及途径。在前期建立的临床患者数据库基础上，采用混合队列评估DEPs暴露水平对EB患者EoP原位分化及症状复发的影响。最终阐明EB的发病机制并揭示DEPs的健康效应。

Eosinophilic bronchitis (EB) is one of the most common causes of chronic cough in China. Its prevalence is much higher than that in Europe and US. The majority of EB are not atopic, which indicates that the Th2 pathway might not play a key role in airway eosinophilic inflammation in EB. However, the mechanism of EB remains unclear. Diesel exhaust particles (DEPs) is the most important source of urban atmospheric PM2.5 and could induce cough，and non-allergic eosinophilic inflammation in murine models as well. Since eosinophil progenitors (EoP) can differentiate into mature eosinophil through in-situ differentiation in the airway. We hypothesize that type 2 innate lymphoid cell (ILC2)-induced in-situ differentiation of EoP play a role in the pathogenesis of EB. Firstly, in different phenotypic patients with EB, the level of in-situ differentiation of EoP in airway would be investigated, as well as its relationship with the ILC2 level. Besides, using a co-culture system of ILC2 and epithelium cells, combining with the DEPs exposure experiment in mice, how DEPs inducing airway eosinophilic inflammation through ILC2 -induced in-situ differentiation of EoP will be explored in series vivo and vitro studies. Finally, a mixed cohort study, based on the established clinical database, will be performed to evaluate the effect of DEPS exposure on EB relapse and in-situ differentiation of EoP through a cox proportional hazards model.All above will be useful to explain the pathogenesis of EB and reveal the effects of DEPs on chronic airway diseases.