ArticleNature communications2024
IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed.
- CTLA4-Ig + Anti-IL-6/IL-6R Treatment Results in Long-term Allograft Survival and Function in Highly HLA-sensitized Patients.Transplantation direct · 2026Article
- Quercetin derived extracellular vesicles combined with ROS responsive hydrogel for diverse damaged tissues repair.Journal of nanobiotechnology · 2026Article
- Regulatory T cells in cardiac allograft vasculopathy: from mechanistic insights to clinical tolerance.Frontiers in immunology · 2026Review
- METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells.Cancer medicine · 2025Article
- Tocilizumab Treatment for Microvascular Inflammation and Chronic Active Antibody-mediated Rejection in Kidney Transplantation.Transplantation direct · 2025Article
- Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity.Current opinion in immunology · 2025Review
- Review
- Interferon-β and interleukin-6 exert opposing effects on Foxp3 acetylation to control regulatory T cell induction.Frontiers in immunology · 2025Article
- Immunosuppression Management in Heart Transplantation.Methodist DeBakey cardiovascular journal · 2025Review
- Case Report: Successful treatment of steroid- and ruxolitinib-refractory gastrointestinal acute graft-versus-Host disease with anti-thymocyte globulin.Frontiers in immunology · 2025Article
- Belatacept in Kidney Transplantation: Reflecting on the Past, Shaping the Future.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The efficacy of costimulation blockade with CTLA4-Ig (belatacept) in transplantation is limited due to T cell-mediated rejection, which also persists after induction with anti-thymocyte globulin (ATG). Here, we investigate why ATG fails to prevent costimulation blockade-resistant rejection and how this barrier can be overcome. ATG did not prevent graft rejection in a murine heart transplant model of CTLA4-Ig therapy and induced a pro-inflammatory cytokine environment. While ATG improved the balance between regulatory T cells (Treg) and effector T cells in the spleen, it had no such effect within cardiac allografts. Neutralizing IL-6 alleviated graft inflammation, increased intragraft Treg frequencies, and enhanced intragraft IL-10 and Th2-cytokine expression. IL-6 blockade together with ATG allowed CTLA4-Ig therapy to achieve long-term, rejection-free heart allograft survival. This beneficial effect was abolished upon Treg depletion. Combining ATG with IL-6 blockade prevents costimulation blockade-resistant rejection, thereby eliminating a major impediment to clinical use of costimulation blockers in transplantation.
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Registered trials
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