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 SP - 2000404 AU - Jie-Sen周盟-周洋李盟Xu-Chen徐AU - Yun赵盟勇王盟Hai-Pin陈盟- Min张盟Yin-Fang吴盟- Tian-Wen赖盟Chun-Hong迪盟-玲玲侗族非盟-胡安刘盟Nan-Xia宣AU -陈竺盟严萍吴盟Hua-Qiong黄盟- Fu-Gui燕盟温家宝华盟-易王盟Wei-Ning Xiong盟回族邱AU -陈道盟东翁盟Hui-Ping李盟-刘晓波周盟撒谎王盟-方刘盟鑫林盟Song-Min应非盟-温李盟Mitsuru导演今村昌平AU -玛丽·e·崔崔AU -马丁·r·Stampfli AU -奥古斯汀表示抗议沈盟- Zhi-Hua陈盟Hua-Hao Y1 - 2020/09/01 UR - //www.qdcxjkg.com/content/56/3/2000404.abstract N2 -目前不明白是否吸烟暴露促进对自身抗原的致敏，以及随后的自身反应性T细胞是否驱动慢性阻塞性肺疾病(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。休息2周后，小鼠气管内注射弹性蛋白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。合成人GVAPGVGVAPGV/HLA-A*02:01四聚体，以评估弹性蛋白特异性T细胞在COPD患者中的存在。我们观察到，2周的香烟烟雾暴露诱导弹性蛋白特异性T细胞反应，导致中性粒细胞气道炎症和弹性蛋白召回挑战后粘液过量产生。1个月的反复弹性蛋白刺激导致气道重塑、肺功能下降和气道扩张。弹性蛋白特异性T细胞回忆反应是剂量依赖性的，记忆持续超过6个月。过继T细胞转移和对T细胞缺陷Rag1−/−小鼠的研究表明，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 -