ArticleThe Journal of clinical investigation2024
Dysregulated Treg repair responses lead to chronic rejection after heart transplantation.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The trial behind it
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Who cites it
17 citing papers in PubMed.
- Single Cell Multi-Omics Revealing the Important Role of MR1 Mediated MAIT Cells in Maintaining Rejection for Liver Transplantation.Cell proliferation · 2026Article
- Review
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.Nature immunology · 2026Article
- IL-2 mutein promotes antigen-specific transplant acceptance in mice through expansion of ST2Nature communications · 2026Article
- Regulatory T cell attracting therapy accelerates skeletal muscle functional recovery following injury.Scientific reports · 2026Article
- Single-cell and spatial transcriptomics identify immune-stromal interactions in cardiac allograft vasculopathy.Nature cardiovascular research · 2026Article
- Fibroblast-derived alarmin promotes oral wound healing by activating regulatory T cells that relay pro-angiogenic and anti-inflammatory responses.Cell reports · 2026Article
- Regulatory T cell therapy in solid organ transplantation: mechanisms, translational progress, and remaining barriers.Frontiers in immunology · 2026Review
- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- Mesenchymal Stem Cells Modulate Regulatory T Cells: From Molecular Mechanisms to Disease Therapy.Stem cells international · 2026Review
- Stimuli-responsive hydrogels based on cascade reactions: a novel strategy to promote the efficient repair of diabetic wounds.Theranostics · 2026Review
- Blocking AREG-EGFR signaling attenuates pan-arterial fibrosis in chronic cardiac allograft rejection.Theranostics · 2026Article
- A stage-based framework to interpret regulatory T cell biology after heart transplantation.Frontiers in cardiovascular medicine · 2026Review
- The DBC1-HIF-1α-PPAR-γ axis regulates Treg cell differentiation to promote myocardial fibrosis in experimental diabetic cardiomyopathy through the paracrine secretion of Areg.Frontiers in endocrinology · 2026Article
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.bioRxiv : the preprint server for biology · 2025Article
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Iron and energy metabolic interactions in Treg-mediated immune regulation.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
Chronic rejection (CR) after organ transplantation is alloimmune injury manifested by graft vascular remodeling and fibrosis that is resistant to immunosuppression. Single-cell RNA-Seq analysis of MHC class II-mismatched (MHCII-mismatched) heart transplants developing chronic rejection identified graft IL-33 as a stimulator of tissue repair pathways in infiltrating macrophages and Tregs. Using IL-33-deficient donor mice, we show that graft fibroblast-derived IL-33 potently induced amphiregulin (Areg) expression by recipient Tregs. The assessment of clinical samples also confirmed increased expression of Areg by intragraft Tregs also during rejection. Areg is an EGF secreted by multiple immune cells to shape immunomodulation and tissue repair. In particular, Areg is proposed to play a major role in Treg-mediated muscle, epithelium, and nerve repair. Assessment of recipient mice with Treg-specific deletion of Areg surprisingly uncovered that Treg secretion of Areg contributed to CR. Specifically, heart transplants from recipients with Areg-deficient Tregs showed less fibrosis, vasculopathy, and vessel-associated fibrotic niches populated by recipient T cells. Mechanistically, we show that Treg-secreted Areg functioned to increase fibroblast proliferation. In total, these studies identify how a dysregulated repair response involving interactions between IL-33+ fibroblasts in the allograft and recipient Tregs contributed to the progression of CR.
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Registered trials
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