HMGB1诱导NETs 导致多发性肌炎/皮肌炎相关间质性肺疾病的分子机制研究

多发性肌炎/皮肌炎(PM/DM) 是一组常见的系统性自身免疫性肌病，间质性肺疾病(ILD)是其最主要合并症，是造成患者死亡的主要因素。我们前期研究首次发现HMGB1及NETs与PM/DM相关性间质性肺疾病(PM/DM-ILD)密切相关，但其机制不清。因此，拟从PM/DM-ILD患者支气管肺泡灌洗液（BALF）来源的中性粒细胞入手，围绕HMGB1-NETs-肺脏靶器官损害，探讨：1）初治PM/DM-ILD的BALF及肺组织中HMGB1表达与NETs形成。2) 揭示HMGB1对PM/DM-ILD BALF中性粒细胞NETs与ILD密切相关的炎性因子的影响及其信号转导机制。3) HMGB1诱导增加的NETs对人肺成纤维细胞发生纤维化影响及机制。本项目将系统研究HMGB1调控NETs在PM/DM--ILD中的分子机制，为PM/DM-ILD的诊断和防治，以及寻求特异性干预靶点提供新的思路。

Polymyositis/Dermatomyositis (PM/DM) is a common systemic autoimmune myopathy. As in PM/DM, interstital lung disease is the most complication, leading to irreversible injury and death in PM/DM. Our earlier study has revealed the association of HMGB1 and PM/DM-ILD, however, the mechanism has not been fully defined. The project will focus on HMGB1-NETs-organ impairment in neutrophils from bronchoalveolar lavage fluid (BALF) in PM/DM-ILD patients. We aim to clarify 1) the changes of HMGB1 and NETs in BALF and pulmonary tissue in PM/DM-ILD; 2) the effects and mechanisms of HMGB1 on NETs and inflammation cytokines in neutrophils from BALF in PM/DM-ILD; 3) the impact and regulation of HMGB1-induced NETs on pulmonary fibrosis.These findings will demonstrate not only a critical avenue of HMGB1 on NETs in PM/DM-ILD but also therapeutic potential targets for the prevention and treatmentin PM/DM-ILD.