突破传统思维定式：固有淋巴样2型细胞的新功能及其在哮喘急性加重中的作用

哮喘是严重威胁公众健康的慢性气道异质性疾病。固有淋巴样2型细胞（ILC2）是近年发现的一种固有免疫细胞，目前认为其与宿主寄生虫防御、过敏性疾病等密切相关。本课题组发现鼻腔吸入IL-33或CXCL16可诱导小鼠ILC2细胞定向聚集于肺和引流淋巴结，并首次发现ILC2细胞具有尚未曾报道的吞噬杀菌新功能，其机制可能是通过吞噬消化、脱颗粒和形成胞外诱捕网（ILC2ETs）的方式对病原体产生杀伤效应。因此，课题组认为ILC2细胞的这种潜能使其在肺脏局部、气道弥散淋巴组织和引流淋巴结的区域性免疫中发挥未知的作用，调控该细胞及其上游分子可能是有效减缓哮喘急性加重和重症哮喘的重要途径。本课题将通过体内外实验体系，阐明调节ILC2细胞产生抗感染免疫功能特别是形成ILC2ETs的分子机制；探索ILC2细胞在介导哮喘急性加重中的作用，从而为揭示哮喘的发病机制以及制定相应的干预治疗策略提供新的实验依据。

Asthma is a heterogeneous chronic airways disease that seriously threats to public health. Group 2 innate lymphoid cells (ILC2) are a type of innate immune cells discovered in recent years and are currently considered to mainly participate in host parasite defense, allergic diseases, and etc. Our group found that nasal inhalation of IL-33 or CXCL16 induced the localization of mouse ILC2 cells in the lung and draining lymphoid organs, and found that new phagocytotic function of ILC2 cells, which has not yet reported. The mechanisms of new function of ILC2 may be through phagocytosis, degranulation and the formation of extracellular traps (here named ILC2ETs), which will produce killing effects on pathogens. Therefore, it is reasonable to hypothesize that the ILC2s play an unknown role, through their potentials in recognizing, processing and treating pathogens, in regional immunity, airway diffuse lymphoid tissue, and regional immunity of draining lymph nodes. Regulation of the cells and its upstream molecules may be a major pathway for slowing down acute exacerbation of asthma and severe asthma effectively. Through in vitro and in vivo experimental systems, the present project will 1) identify the mechanism of formation of ILC2ETs and similarity/differences in composition and function compared with known extracellular traps; 2) elucidate the regulation of molecular mechanism of the production of anti-infective immune function by ILC2 cells; and 3) explore the role of ILC2 cells in acute exacerbation of asthma. We hope that the present study provides a new experimental basis for revealing the pathogenesis of asthma and developing appropriate intervention strategies.