闭塞性细支气管炎
肺
免疫学
医学
CD8型
免疫抑制
肺移植
癌症研究
生物
免疫系统
病理
内科学
作者
Zhiyi Liu,Fuyi Liao,Davide Scozzi,Yasubumi Furuya,Kaitlyn N. Pugh,Ramsey R. Hachem,Delphine L. Chen,Marlene Cano,Jonathan M. Green,Alexander S. Krupnick,Daniel Kreisel,Anne‐Karina T. Perl,Howard J. Huang,Steven L. Brody,Andrew E. Gelman
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2019-04-16
卷期号:4 (9)
被引量:23
标识
DOI:10.1172/jci.insight.124732
摘要
Obliterative bronchiolitis (OB) is a poorly understood airway disease characterized by the generation of fibrotic bronchiolar occlusions. In the lung transplant setting, OB is a pathological manifestation of bronchiolitis obliterans syndrome (BOS), which is a major impediment to long-term recipient survival. Club cells play a key role in bronchiolar epithelial repair, but whether they promote lung transplant tolerance through preventing OB remains unclear. We determined if OB occurs in mouse orthotopic lung transplants following conditional transgene-targeted club cell depletion. In syngeneic lung transplants club cell depletion leads to transient epithelial injury followed by rapid club cell-mediated repair. In contrast, allogeneic lung transplants develop severe OB lesions and poorly regenerate club cells despite immunosuppression treatment. Lung allograft club cell ablation also triggers the recognition of alloantigens, and pulmonary restricted self-antigens reported associated with BOS development. However, CD8+ T cell depletion restores club cell reparative responses and prevents OB. In addition, ex-vivo analysis reveals a specific role for alloantigen-primed effector CD8+ T cells in preventing club cell proliferation and maintenance. Taken together, we demonstrate a vital role for club cells in maintaining lung transplant tolerance and propose a new model to identify the underlying mechanisms of OB.
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