TY - T1的香烟smoke-initiated自身免疫促进敏化作用,elastin-induced COPD-like病态老鼠JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00404 -2020欧元六世- 56 - 3周SP - 2000404 AU, Jie-Sen AU -李,周洋盟——徐Xu-Chen盟——赵,永盟- Chen Yun AU - Wang Hai-Pin盟——张,分盟,吴Yin-Fang AU -赖,Tian-Wen AU - Di, Chun-Hong盟——咚,玲玲盟——刘,胡安盟——宣Nan-Xia盟——朱、陈盟,吴严萍AU -黄,Hua-Qiong盟——燕,Fu-Gui盟——华,温家宝AU -王,易盟——熊Wei-Ning盟——秋,回族盟——陈道盟-翁,Hui-Ping盟,周董盟- Li刘晓波AU -王,谎言盟——刘,方非盟-林,鑫盟——应Song-Min AU -李,温家宝盟——导演今村昌平,Mitsuru AU -崔,玛丽e . AU - Stampfli马丁·r . AU -崔奥古斯汀表示抗议AU - Chen Zhi-Hua盟,沈Hua-Hao Y1 - 2020/09/01 UR - //www.qdcxjkg.com/content/56/3/2000404.abstract N2 -目前尚不清楚香烟烟雾暴露是否会促进对自身抗原的敏感，以及随后的自动反应性T细胞是否会导致慢性阻塞性肺疾病(COPD)相关病理。为了解决这个问题，老鼠被暴露在香烟烟雾中2周。在休息2周后，小鼠气管内注射弹性蛋白，持续3天或1个月。Rag1−/−、Mmp12−/−和Il17a−/−小鼠和针对活性弹性蛋白片段的中和抗体用于机制研究。人类GVAPGVGVAPGV/HLA-A*02:01四聚体被合成用于评估COPD患者中弹性蛋白特异性T细胞的存在。我们观察到2周的香烟烟雾暴露诱导了弹性蛋白特异性T细胞反应，导致中性粒细胞性气道炎症和弹性蛋白回忆挑战后粘液增生。弹性蛋白反复挑战1个月，导致气道重塑，肺功能下降，气道扩大。弹性蛋白特异性T细胞回忆反应是剂量依赖性的，记忆持续6个月以上。过继T细胞转移和对缺乏Rag1−/−的T细胞小鼠的研究最终表明T细胞参与了这些过程。 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 ER -