ArticleJCI insight2019
A20 as an immune tolerance factor can determine islet transplant outcomes.
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 23 papers.
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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
23 citing papers in PubMed, 35 citations in OpenAlex.
- The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Cell Therapy for Type 1 Diabetes Mellitus: a Review of Clinical Trials.Bulletin of experimental biology and medicine · 2025Review
- Article
- Mesenchymal stromal cells and their secretory products reduce the inflammatory crosstalk between islets and endothelial cells.Endocrine · 2025Article
- Gene therapy for polygenic or complex diseases.Biomarker research · 2024Review
- Engineering Pancreatic Islets to Transiently Codisplay on Their Surface Thrombomodulin and CD47 Immunomodulatory Proteins as a Means of Mitigating Instant Blood-Mediated Inflammatory Reaction following Intraportal Transplantation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Long-Term Survival and Induction of Operational Tolerance to Murine Islet Allografts by Co-Transplanting Cyclosporine A Microparticles and CTLA4-Ig.Pharmaceutics · 2023Article
- RELA governs a network of islet-specific metabolic genes necessary for beta cell function.Diabetologia · 2023Article
- Sertoli Cells Express Accommodation, Survival, and Immunoregulatory Factors When Exposed to Normal Human Serum.Biomedicines · 2023Article
- Prevention of Type 1 Diabetes in Children: A Worthy Challenge?International journal of environmental research and public health · 2023Review
- Engineering pancreatic islets with a novel form of thrombomodulin protein to overcome early graft loss triggered by instant blood-mediated inflammatory reaction.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Article
- Advancements in innate immune regulation strategies in islet transplantation.Frontiers in immunology · 2023Review
- Case Report: A novel mutation inFrontiers in endocrinology · 2023Article
- TNFAIP3 Reduction-of-Function Drives Female Infertility and CNS Inflammation.Frontiers in immunology · 2022Article
- Immune-Protective Formulations and Process Strategies for Improved Survival and Function of Transplanted Islets.Frontiers in immunology · 2022Review
- Genetic Engineering of Immune Evasive Stem Cell-Derived Islets.Transplant international : official journal of the European Society for Organ Transplantation · 2022Review
- Restoring normal islet mass and function in type 1 diabetes through regenerative medicine and tissue engineering.The lancet. Diabetes & endocrinology · 2021Review
- Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Withaferin A inhibits lymphocyte proliferation, dendritic cell maturation in vitro and prolongs islet allograft survival.Scientific reports · 2021Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Islet transplantation can restore lost glycemic control in type 1 diabetes subjects but is restricted in its clinical application by a limiting supply of islets and the need for heavy immune suppression to prevent rejection. TNFAIP3, encoding the ubiquitin editing enzyme A20, regulates the activation of immune cells by raising NF-κB signaling thresholds. Here, we show that increasing A20 expression in allogeneic islet grafts resulted in permanent survival for ~45% of recipients, and > 80% survival when combined with subtherapeutic rapamycin. Allograft survival was dependent upon Tregs and was antigen specific, and grafts showed reduced expression of inflammatory factors. Transplantation of islets with A20 containing a loss-of-function variant (I325N) resulted in increased RIPK1 ubiquitination and NF-κB signaling, graft hyperinflammation, and acute allograft rejection. Overexpression of A20 in human islets potently reduced expression of inflammatory mediators, with no impact on glucose-stimulated insulin secretion. Therapeutic administration of A20 raises inflammatory signaling thresholds to favor immune tolerance and promotes islet allogeneic survival. Clinically, this would allow for reduced immunosuppression and support the use of alternate islet sources.
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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.