RT期刊文章SR电子香烟smok T1e-initiated autoimmunity facilitates sensitisation to elastin-induced COPD-like pathologies in mice JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2000404 DO 10.1183/13993003.00404-2020 VO 56 IS 3 A1 Zhou, Jie-Sen A1 Li, Zhou-Yang A1 Xu, Xu-Chen A1 Zhao, Yun A1 Wang, Yong A1 Chen, Hai-Pin A1 Zhang, Min A1 Wu, Yin-Fang A1 Lai, Tian-Wen A1 Di, Chun-Hong A1 Dong, Ling-Ling A1 Liu, Juan A1 Xuan, Nan-Xia A1 Zhu, Chen A1 Wu, Yan-Ping A1 Huang, Hua-Qiong A1 Yan, Fu-Gui A1 Hua, Wen A1 Wang, Yi A1 Xiong, Wei-Ning A1 Qiu, Hui A1 Chen, Tao A1 Weng, Dong A1 Li, Hui-Ping A1 Zhou, Xiaobo A1 Wang, Lie A1 Liu, Fang A1 Lin, Xin A1 Ying, Song-Min A1 Li, Wen A1 Imamura, Mitsuru A1 Choi, Mary E. A1 Stampfli, Martin R. A1 Choi, Augustine M.K. A1 Chen, Zhi-Hua A1 Shen, Hua-Hao YR 2020 UL //www.qdcxjkg.com/content/56/3/2000404.abstract AB It is currently not understood whether cigarette smoke exposure facilitates sensitisation to self-antigens and whether ensuing auto-reactive T cells drive chronic obstructive pulmonary disease (COPD)-associated pathologies.To address this question, mice were exposed to cigarette smoke for 2 weeks. Following a 2-week period of rest, mice were challenged intratracheally with elastin for 3 days or 1 month. Rag1−/−, Mmp12−/−, and Il17a−/− mice and neutralising antibodies against active elastin fragments were used for mechanistic investigations. Human GVAPGVGVAPGV/HLA-A*02:01 tetramer was synthesised to assess the presence of elastin-specific T cells in patients with COPD.We observed that 2 weeks of cigarette smoke exposure induced an elastin-specific T cell response that led to neutrophilic airway inflammation and mucus hyperproduction following elastin recall challenge. Repeated elastin challenge for 1 month resulted in airway remodelling, lung function decline and airspace enlargement. Elastin-specific T cell recall responses were dose dependent and memory lasted for over 6 months. Adoptive T cell transfer and studies in T cells deficient Rag1−/−mice conclusively implicated T cells in these processes. Mechanistically, cigarette smoke exposure-induced elastin-specific T cell responses were matrix metalloproteinase (MMP)12-dependent, while the ensuing immune inflammatory processes were interleukin 17A-driven. Anti-elastin antibodies and T cells specific for elastin peptides were increased in patients with COPD.These data demonstrate that MMP12-generated elastin fragments serve as a self-antigen and drive the cigarette smoke-induced autoimmune processes in mice that result in a bronchitis-like phenotype and airspace enlargement. The study provides proof of concept of cigarette smoke-induced autoimmune processes and may serve as a novel mouse model of COPD.MMP12-generated elastin fragments serve as a self-antigen and drive cigarette smoke-induced autoimmune processes in mice. These findings provide experimental evidence for cigarette smoke-induced autoimmunity and represent a novel mouse model of COPD. https://bit.ly/2XK9dC6