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,云非盟- Wang Yong盟——陈Hai-Pin AU -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,严萍盟——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,欧列刘、欧芳林、欧新英、欧松民李、欧文今村、欧密如、欧美如、欧美如Stampfli、欧芳如、欧古斯丁M.K.欧陈、欧志华欧申、Hua-Hao Y1 - 2020/09/01 UR - //www.qdcxjkg.com/content/56/3/2000404.abstract N2 -目前尚不清楚暴露在香烟烟雾中是否会促进对自身抗原的敏感性，以及随后产生的自体反应性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，小鼠暴露在香烟烟雾中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*02:01四聚体来评估COPD患者中弹性蛋白特异性T细胞的存在。我们观察到，暴露在香烟烟雾中2周后，会诱发弹性蛋白特异性T细胞反应，导致中性粒细胞性气道炎症和黏液分泌过剩。反复激发弹性蛋白1个月，气道重构，肺功能下降，气道扩大。弹性蛋白特异性T细胞回忆反应具有剂量依赖性，记忆持续时间超过6个月。 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 ER -