ArticleDiabetes2013
β-cell-specific IL-2 therapy increases islet Foxp3+Treg and suppresses type 1 diabetes in NOD mice.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02772679 (A Phase 1 Trial of CD4+CD127lo/-CD25+ Polyclonal Treg Adoptive Immunotherapy With Interleukin-2 for the Treatment of Type 1 Diabetes), which is not on this map. Cited by 28 papers.
What it found
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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.
A Phase 1 Trial of CD4+CD127lo/-CD25+ Polyclonal Treg Adoptive Immunotherapy With Interleukin-2 for the Treatment of Type 1 Diabetes
Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Impact of Soluble Schistosomal Egg Antigens on Type 1 Diabetes Mellitus in an Induced Diabetic Mouse Model.Acta parasitologica · 2025Article
- A comprehensive atlas of AAV tropism in the mouse.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Regulatory T cell dysfunction and immunotherapeutic breakthroughs in type 1 diabetes.Frontiers in endocrinology · 2025Review
- The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.JCI insight · 2024Article
- SOCS3 inhibits the mesenchymal stromal cell secretory factor SDF-1-mediated improvement of islet function in non-obese diabetic mice.Stem cell research & therapy · 2023Article
- Combinatorial islet protective therapeutic approaches in β-cell transplantation: Rationally designed solutions using a target product profile.FASEB bioAdvances · 2023Review
- Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies.Diabetes · 2023Article
- Gene Delivery of Manf to Beta-Cells of the Pancreatic Islets Protects NOD Mice from Type 1 Diabetes Development.Biomolecules · 2022Article
- The emerging role of regulatory cell-based therapy in autoimmune disease.Frontiers in immunology · 2022Review
- Autoimmune thyroid disease and type 1 diabetes mellitus: same pathogenesis; new perspective?Therapeutic advances in endocrinology and metabolism · 2020Review
- The Role of T Cell Receptor Signaling in the Development of Type 1 Diabetes.Frontiers in immunology · 2020Review
- The promise of CD4Haematologica · 2019Review
- Helminths protect against type 1 diabetes: effects and mechanisms.Parasitology research · 2019Review
- Lack of acute xenogeneic graft- versus-host disease, but retention of T-cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Gene Therapy with an Adeno-Associated Viral Vector Expressing Human Interleukin-2 Alters Immune System Homeostasis in Humanized Mice.Human gene therapy · 2018Article
- Self-Transducible Bimodal PDX1-FOXP3 Protein Lifts Insulin Secretion and Curbs Autoimmunity, Boosting Tregs in Type 1 Diabetic Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Therapies to Suppress β Cell Autoimmunity in Type 1 Diabetes.Frontiers in immunology · 2018Review
- LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes.Science immunology · 2017Article
- The contribution of interleukin-2 to effective wound healing.Experimental biology and medicine (Maywood, N.J.) · 2017Review
- T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes.Frontiers in endocrinology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-2 (IL-2) is a critical cytokine for the homeostasis and function of forkhead box p3-expressing regulatory T cells (Foxp3(+)Tregs). Dysregulation of the IL-2-IL-2 receptor axis is associated with aberrant Foxp3(+)Tregs and T cell-mediated autoimmune diseases such as type 1 diabetes. Treatment with recombinant IL-2 has been reported to enhance Foxp3(+)Tregs and suppress different models of autoimmunity. However, efficacy of IL-2 therapy is dependent on achieving sufficient levels of IL-2 to boost tissue-resident Foxp3(+)Tregs while avoiding the potential toxic effects of systemic IL-2. With this in mind, adeno-associated virus (AAV) vector gene delivery was used to localize IL-2 expression to the islets of NOD mice. Injection of a double-stranded AAV vector encoding IL-2 driven by a mouse insulin promoter (dsAAVmIP-IL2) increased Foxp3(+)Tregs in the islets but not the draining pancreatic lymph nodes. Islet Foxp3(+)Tregs in dsAAVmIP-IL2-treated NOD mice exhibited enhanced fitness marked by increased expression of Bcl-2, proliferation, and suppressor function. In contrast, ectopic IL-2 had no significant effect on conventional islet-infiltrating effector T cells. Notably, β-cell-specific IL-2 expression suppressed late preclinical type 1 diabetes in NOD mice. Collectively, these findings demonstrate that β-cell-specific IL-2 expands an islet-resident Foxp3(+)Tregs pool that effectively suppresses ongoing type 1 diabetes long term.
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What OpenQuestion holds
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.