现代工农业生产的飞速发展使相关职业劳动者长期暴露于复杂的有机粉尘污染环境。高浓度真菌污染所引起的过敏性肺炎等免疫性肺疾病受到越来越广泛的关注。其基本病理特征是肺间质炎性细胞浸润和肉芽肿。但目前其发病机制尚不清楚。前期研究表明中性粒细胞在过敏性肺炎中发挥重要的调控作用。近年来，自噬因可通过维持细胞内环境动态平衡调控细胞功能而成为研究热点。中性粒细胞自噬水平的变化直接影响其免疫调控功能的发挥。HMGB1可诱导细胞自噬并调控多种疾病。但HMGB1在过敏性肺炎中的作用尚不清楚，HMGB1依赖性自噬调控中性粒细胞功能的具体机制尚未明确。本实验拟以真菌细胞壁主要成分1,3-β-葡聚糖所致的小鼠肺部炎症为模型，利用条件性基因敲除及消除抗体等手段，从细胞、分子水平探讨HMGB1信号通路及中性粒细胞HMGB1依赖性自噬调控过敏性肺炎的免疫学分子机制。旨在为职业性过敏性肺炎的治疗及预后提供新的免疫分子靶标。

The rapid development of modern industrial and agricultural production brings related occupational workers the sever exposure to the complex organic dust contaminated environment. The high-dose fugues contamination induced hypersensitivity pneumonitis draws an increasingly wide attention. The fundamental pathological characters are the inflammatory cells accumulation in lung parenchyma and the formation of granuloma. However, the mechanism of the immunological modulation during the pathology process is not still clearly demonstrated. Our previous research demonstrated the critical role of neutrophils in regulating the process of hypersensitivity pneumonitis. Autophagy contributes to maintain the dynamic balance in intercellular environment and is becoming the research hotspot. The transformation of neutrophil autophagy could directly affect its immune regulatory function. High mobility group box-1 protein (HMGB1) could induce autophagy and play a regulatory role in multiple diseases. However, the actual role of HMGB1 signal pathway in the development of hypersensitivity pneumonitis is not clear. The detailed mechanism of HMGB1-dependent autophagy in regulating neutrophils function need further investigation. Our project was aimed at illustrating the immune molecular mechanisms of the HMGB1 signal pathway and HMGB1-dependent autophagy of neutrophils in hypersensitivity pneumonitis at both cellular and molecular levels by using conditional knockout mice and neutralizing antibody. The major constructive composition of fugues 1-3-β-glucan will be used to setup mice pulmonary inflammation model. It is believed that if we demonstrated the molecular regulatory mechanisms of HMGB1-dependent autophagy of neutrophils in hypersensitivity pneumonitis successfully, the innovative immune molecular targets will be provided to contribute to the treatment and prognosis of occupational hypersensitivity pneumonitis.