迷走神经调控哮喘肺部区域免疫的特点和机制

支气管哮喘，尤其是病理上以非嗜酸粒细胞浸润为主的难治性哮喘，严重威胁人民的生命健康。我们已有的实验数据表明气道上皮细胞来源的外泌体可能在气道上皮细胞、免疫细胞、气道稀有细胞（Tuft和PNECs）和ILC2间进行通讯，诱发以中性/单核粒细胞为主的气道炎症。迷走神经有可能通过α7 nAChR和神经肽来影响气道上皮细胞来源的外泌体的生成和功能，进而影响肺巨噬细胞、PNECs、Tuft和ILC2细胞的功能来调控哮喘形成。本项目将应用分子生物学、免疫学、神经生理学、转录和蛋白组学等先进手段来深入迷走神经调控哮喘发生的肺部区域免疫特点，阐明神经调控哮喘时外泌体免疫细胞间通讯的分子机制，帮助我们找到参与哮喘发生和修复的新理论和作用靶点，研究成果将具有重大的临床应用价值。

Asthma, especially refractory asthma with pathologically non-eosinophilic infiltration, is a serious threat to people's lives and health. Our primary experimental data have indicated that airway epithelial cell-derived exosomes may communicate among airway epithelial cells, immune cells, airway rare cells (Tuft and PNECs), and ILC2, inducing airway inflammation dominated by neutrophil/monoctye infiltration. The vagus nerve may regulate the biogenesis and function of airway epithelial cell-derived exosomes through α7 nAChR and neuropeptides, thereby affecting the function of lung macrophages, PNECs, Tuft and ILC2 cells to determine the pathogenesis of asthma. This project will take advantage of the state-of-art technology such as molecular biology, immunology, neurophysiology, transcriptomics, and proteomics to reveal the vagus nerve-regulated characteristics of lung regional immunity，elucidate the neural regulatory mechanism of exosomes in cellular communication, and develop novel theories and therapeutic targets for fighting refractory asthma. The research results will have a significant clinical application value.