ArticleThe Journal of clinical investigation2020
Graft IL-33 regulates infiltrating macrophages to protect against chronic rejection.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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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
43 citing papers in PubMed, 66 citations in OpenAlex.
- A modified mouse heart transplant model with extended aorta enables analysis of vascular continuity in cardiac allograft vasculopathy.JHLT open · 2026Article
- Tissue-Resident Macrophages: Linking Physiology and Inflammation in Infection.Clinical reviews in allergy & immunology · 2026Review
- Elevated interleukin-33, CD1c+ dendritic cells, and interleukin-17A in peritoneal fluid of patients with endometriosis: a case-control study.Molecular biology reports · 2026Article
- Suppression of cardiac allograft vasculopathy by a macrophage efferocytosis receptor.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Cytokines Associated with Activation of CD4International journal of molecular sciences · 2026Review
- Innovative Insights into Interleukin-Mediated Macrophage Polarization: Metabolic Reprogramming and Inflammatory Pathway Crosstalk in Chronic Kidney Disease and Therapeutic Implications-A Narrative Review.International journal of general medicine · 2026Review
- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- Setdb1 ablation in macrophages attenuates fibrosis in heart allografts.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Immunometabolism of Liver Xenotransplantation and Prospective Solutions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Cardiac matrix-bound Nanovesicles provide insight into mechanisms of clinical heart disease progression to failure.International journal of cardiology · 2025Article
- The role of macrophages in the mitigation by decitabine of acute allograft rejection.Frontiers in transplantation · 2025Article
- Dysregulated Treg repair responses lead to chronic rejection after heart transplantation.The Journal of clinical investigation · 2024Article
- Partial reduction of interleukin-33 signaling improves senescence and renal injury in diabetic nephropathy.MedComm · 2024Article
- IL-33/ST2 signaling in monocyte-derived macrophages maintains blood-brain barrier integrity and restricts infarctions early after ischemic stroke.Journal of neuroinflammation · 2024Article
- 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
- Inflammation accelerating intestinal fibrosis: from mechanism to clinic.European journal of medical research · 2024Review
- TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway in mice.Cell death & disease · 2024Article
- AXL inhibition suppresses early allograft monocyte-to-macrophage differentiation and prolongs allograft survival.JCI insight · 2024Article
- Matrix-bound nanovesicle-associated IL-33 supports functional recovery after skeletal muscle injury by initiating a pro-regenerative macrophage phenotypic transition.NPJ Regenerative medicine · 2024Article
- Dendritic Cell-Derived Exosomes Promote Tendon Healing and Regulate Macrophage Polarization in Preventing Tendinopathy.International journal of nanomedicine · 2024Article
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
Abstract
Alarmins, sequestered self-molecules containing damage-associated molecular patterns, are released during tissue injury to drive innate immune cell proinflammatory responses. Whether endogenous negative regulators controlling early immune responses are also released at the site of injury is poorly understood. Herein, we establish that the stromal cell-derived alarmin interleukin 33 (IL-33) is a local factor that directly restricts the proinflammatory capacity of graft-infiltrating macrophages early after transplantation. By assessing heart transplant recipient samples and using a mouse heart transplant model, we establish that IL-33 is upregulated in allografts to limit chronic rejection. Mouse cardiac transplants lacking IL-33 displayed dramatically accelerated vascular occlusion and subsequent fibrosis, which was not due to altered systemic immune responses. Instead, a lack of graft IL-33 caused local augmentation of proinflammatory iNOS+ macrophages that accelerated graft loss. IL-33 facilitated a metabolic program in macrophages associated with reparative and regulatory functions, and local delivery of IL-33 prevented the chronic rejection of IL-33-deficient cardiac transplants. Therefore, IL-33 represents what we believe is a novel regulatory alarmin in transplantation that limits chronic rejection by restraining the local activation of proinflammatory macrophages. The local delivery of IL-33 in extracellular matrix-based materials may be a promising biologic for chronic rejection prophylaxis.
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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.