ArticleThe Journal of clinical investigation2022
Reprogramming alveolar macrophage responses to TGF-β reveals CCR2+ monocyte activity that promotes bronchiolitis obliterans syndrome.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Alveolar Macrophages: Development, Respiratory Homeostasis, Signal Pathways, Diseases, and Therapeutic Opportunities.MedComm · 2026Review
- Extracorporeal photopheresis: A comprehensive review from a transfusion medicine perspective.Hematology, transfusion and cell therapy · 2026Review
- Chronic graft-versus-host disease.Nature reviews. Disease primers · 2026Review
- Game Changer: Extracorporeal Photopheresis for the Prevention of Rejection After Lung Transplantation-A Prospective Randomized Controlled Trial.Transplantation · 2025Article
- Tolerogenic lung allograft microenvironment suppresses pathogenic tissue remodeling following respiratory virus infection in mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Chronic Graft-versus-host Disease, Part 1: How Preclinical Models Shape Our Understanding of Biology and Pave the Way for Future Therapeutic Interventions.Transplantation · 2025Review
- Moving the needle on chronic GVHD of the lung.Blood advances · 2025Article
- Xcr1eLife · 2025Article
- Extracorporeal Photopheresis: From Animal Models to Clinical Practice.Transplantation direct · 2025Article
- Potential Biomarkers of Therapeutic Response to ECP in Solid Organ Transplantation.Transplantation direct · 2025Article
- Article
- Shared roles of immune and stromal cells in the pathogenesis of human bronchiolitis obliterans syndrome.JCI insight · 2025Article
- Chronic Lung Allograft Dysfunction: Clinical Manifestations and Immunologic Mechanisms.Transplantation · 2025Review
- Tissue-resident immune cells: from defining characteristics to roles in diseases.Signal transduction and targeted therapy · 2025Review
- Monocytosis as prognostic factor for chronic graft versus host disease.Bone marrow transplantation · 2024Article
- Macrophage and CD8 T cell discordance are associated with acute lung allograft dysfunction progression.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Article
- Extracorporeal Photopheresis Reduces Fibrotic and Inflammatory Transcriptomic Biological Marker of Chronic Antibody-mediated Kidney Rejection.Transplantation direct · 2024Article
- Immune dysregulation as a driver of bronchiolitis obliterans.Frontiers in immunology · 2024Review
- IL-17A neutralization fails to attenuate airway remodeling and potentiates a proinflammatory lung microenvironment in diacetyl-exposed rats.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Expansion of ST2-expressing macrophages in a patient with bronchiolitis obliterans syndrome.ERJ open research · 2023Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-β and reduce TGF-β bioavailability through secretion of the TGF-β antagonist decorin. In untreated recipients, high airway TGF-β activity stimulated AMs to express CCL2, leading to CCR2+ monocyte-driven BOS development. Moreover, we found TGF-β receptor 2-dependent differentiation of CCR2+ monocytes was required for the generation of monocyte-derived AMs, which in turn promoted BOS by expanding tissue-resident memory CD8+ T cells that inflicted airway injury through Blimp-1-mediated granzyme B expression. Thus, through studying the effects of ECP, we have identified an AM functional plasticity that controls a TGF-β-dependent network that couples CCR2+ monocyte recruitment and differentiation to alloimmunity and BOS.
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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.