固有淋巴样2型细胞（ILC2）在哮喘发生机制中的作用研究

哮喘是严重威胁公众健康的常见疾病，慢性炎症和气道重塑为其病理特征。近年发现IL-25诱导产生的固有淋巴样2型细胞（ILC2）是参与过敏性疾病和宿主寄生虫防御的免疫效应细胞。本课题组前期研究发现鼻腔吸入IL-25可诱导小鼠气道高反应性，哮喘样气道炎症反应和气道重塑等病理学改变，并伴随Lin-ICOS+T1/ST2variable ILC2细胞在肺内聚集，该细胞通过合成分泌IL-13等生物活性介质导致上述反应的发生。这些结果提示ILC2细胞及其介导的生物学效应是继IL-25作用之后参与哮喘发生发展，引发哮喘慢性炎症和气道重塑的重要原因，在Th2细胞介导的适应性免疫应答过程中起到重要的桥梁作用。本课题利用哮喘模型小鼠，通过流式细胞术、小动物活体成像等技术研究ILC2细胞参与Th2型免疫应答的机制及其与哮喘慢性炎症和气道重塑的关系，以期为阐明哮喘发生机制和新型靶向药物的筛选提供实验依据。

Asthma is a common disease, seriously threatening public health, characterized with chronic airways inflammation and remodeling. ILC2 is recently discovered as a subset of cells, termed as Type 2 innate lymphoid cells, mainly participating in pathogenesis of allergic atopic diseases and parasite defence in host. Our preliminary data showed that nasal inhalation of IL-25 induces airway hyperresponsiveness, airways inflammation and remodeling, companying with accumulation of Lin-ICOS+ T1/ST2variable ILC2 in murine lungs，suggesting that these cells are possibly associated with pathological changes as above, through producing IL-13 and other mediators. These data indicate that the effects of ILC2 and the ILC2-relevant mediators are the consequences of acting of IL-25, which contribute to pathogenesis of asthma, such as chronic airways inflammation and remodeling. These cells may serve as a bridge between innate and adaptive immunities in asthma. Using murine asthma models and a number of techniques such as flow cytometry and in vivo imaging of small animals, we attempt to investigate the mechanisms of ILC2 participating in Th2-mediated responses and to evaluate the relationships between ILC2 and airways chronic inflammation and remodeling in asthma. We hope that the project will provide experimental basis for elucidating the pathogenesis and screen new therapeutic targets for treatment in asthma.