ArticleDiabetes2011
Interleukin-21 is critically required in autoimmune and allogeneic responses to islet tissue in murine models.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Gut microbiota-modulating interventions in paediatric type 1 diabetes: a systematic review and meta-analysis.European journal of pediatrics · 2026Pooled it
- Aberrant IL-21/STAT3 signaling disrupts regulatory T cell function and CD4Frontiers in immunology · 2026Article
- IL-21 mediates crosstalk between T cells and NK cells during the remission of type 1 diabetes.Nature metabolism · 2026Article
- How Cytokines Regulate Immune Response Toward Chronic Allograft Rejection?Results and problems in cell differentiation · 2026Review
- An interleukin-27-centered cytokine circuit regulates macrophage and T cell interactions in autoimmune diabetes.iScience · 2025Article
- Shifting the paradigm of type 1 diabetes: a narrative review of disease modifying therapies.Frontiers in endocrinology · 2024Review
- Heterogeneity of Islet-Infiltrating IL-21+ CD4 T Cells in a Mouse Model of Type 1 Diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Evaluation of plasma IL-21 as a potential biomarker for type 1 diabetes progression.Frontiers in immunology · 2023Article
- New developments implicating IL-21 in autoimmune disease.Journal of autoimmunity · 2021Review
- Current and future therapies for type 1 diabetes.Diabetologia · 2021Review
- An Insulin-Inspired Supramolecular Hydrogel for Prevention of Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Regulation of the germinal center and humoral immunity by interleukin-21.The Journal of experimental medicine · 2020Review
- Evolving Antibody Therapies for the Treatment of Type 1 Diabetes.Frontiers in immunology · 2020Review
- The Role of T Cell Receptor Signaling in the Development of Type 1 Diabetes.Frontiers in immunology · 2020Review
- IL-21 regulates SOCS1 expression in autoreactive CD8Scientific reports · 2019Article
- Interleukin 21 (IL-21) regulates chronic allograft vasculopathy (CAV) in murine heart allograft rejection.PloS one · 2019Article
- Article
- SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes.The Journal of clinical investigation · 2018Article
- Anti-Insulin B Cells Are Poised for Antigen Presentation in Type 1 Diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Therapies to Suppress β Cell Autoimmunity in Type 1 Diabetes.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveType 1 diabetes is an incurable chronic autoimmune disease. Although transplantation of pancreatic islets may serve as a surrogate source of insulin, recipients are subjected to a life of immunosuppression. Interleukin (IL)-21 is necessary for type 1 diabetes in NOD mice. We examined the efficacy of an IL-21-targeted therapy on prevention of diabetes in NOD mice, in combination with syngeneic islet transplantation. In addition, we assessed the role of IL-21 responsiveness in islet allograft rejection in mouse animal models. RESEARCH DESIGN AND
methodsNOD mice were treated with IL-21R/Fc, an IL-21-neutralizing chimeric protein. This procedure was combined with syngeneic islet transplantation to treat diabetic NOD mice. Survival of allogeneic islet grafts in IL-21R-deficient mice was also assessed.
resultsEvidence is provided that IL-21 is continually required by the autoimmune infiltrate, such that insulitis was reduced and reversed and diabetes inhibited by neutralization of IL-21 at a late preclinical stage. Recovery from autoimmune diabetes was achieved by combining neutralization of IL-21 with islet transplantation. Furthermore, IL-21-responsiveness by CD8+ T-cells was sufficient to mediate islet allograft rejection.
conclusionsNeutralization of IL-21 in NOD mice can inhibit diabetes, and when paired with islet transplantation, this therapeutic approach restored normoglycemia. The influence of IL-21 on a graft-mounted immune response was robust, since the absence of IL-21 signaling prevented islet allograft rejection. These findings suggest that therapeutic manipulation of IL-21 may serve as a suitable treatment for patients with type 1 diabetes.
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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.