ArticleJCI insight2019
An obligatory role for club cells in preventing obliterative bronchiolitis in lung transplants.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- B6 Donor Lungs Develop Chronic Lung Allograft Dysfunction-like Pathology Across Histocompatibility Mismatches in Murine Lung Transplantation.Transplantation direct · 2026Article
- Lung cell fates during influenza.Cell research · 2025Review
- Addressing Knowledge Gaps in the Early Detection of Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Chronic Lung Allograft Dysfunction: Clinical Manifestations and Immunologic Mechanisms.Transplantation · 2025Review
- NKG2D blockade impairs tissue-resident memory T cell accumulation and reduces chronic lung allograft dysfunction.JCI insight · 2025Article
- Airway epithelium in lung transplantation: a potential actor for post-transplant complications?European respiratory review : an official journal of the European Respiratory Society · 2024Review
- The multiple facets of the club cell in the pulmonary epithelium.Histology and histopathology · 2024Review
- IL-33: Friend or foe in transplantation?The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Review
- Donor IL-17 receptor A regulates LPS-potentiated acute and chronic murine lung allograft rejection.JCI insight · 2023Article
- Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2023Article
- An update in club cell biology and its potential relevance to chronic obstructive pulmonary disease.American journal of physiology. Lung cellular and molecular physiology · 2023Review
- Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics.Annual review of medicine · 2023Review
- Consequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development.Nature communications · 2022Article
- Reprogramming alveolar macrophage responses to TGF-β reveals CCR2+ monocyte activity that promotes bronchiolitis obliterans syndrome.The Journal of clinical investigation · 2022Article
- Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation.JCI insight · 2022Article
- Characterization of Immunopathology and Small Airway Remodeling in Constrictive Bronchiolitis.American journal of respiratory and critical care medicine · 2022Article
- Airway secretory cell fate conversion via YAP-mTORC1-dependent essential amino acid metabolism.The EMBO journal · 2022Article
- Airway disease in hematologic malignancies.Expert review of respiratory medicine · 2022Review
- Sustained Club Cell Injury in Mice Induces Histopathologic Features of Deployment-Related Constrictive Bronchiolitis.The American journal of pathology · 2022Article
- Lymphocytic Airway Inflammation in Lung Allografts.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.