ArticleDiabetes2013
Limitations of IL-2 and rapamycin in immunotherapy of type 1 diabetes.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a Phase I/II randomised, double-blind, placebo-controlled, dose-finding study.Diabetologia · 2020Trial
- Immunotherapy with low-dose IL-2 attenuates vascular injury in mice with diabetic and neovascular retinopathy by restoring the balance between Foxp3Diabetologia · 2025Article
- Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity.Current opinion in immunology · 2025Review
- Immunotherapies for prevention and treatment of type 1 diabetes.Immunotherapy · 2025Review
- Assessing the effectiveness of Interleukin-2 therapy in experimental type 1 diabetes.Endocrine · 2024Article
- Biomaterials-based nanoparticles conjugated to regulatory T cells provide a modular system for localized delivery of pharmacotherapeutic agents.Journal of biomedical materials research. Part A · 2023Article
- Ginsenoside Rg1 Ameliorates Pancreatic Injuries via the AMPK/mTOR Pathway in vivo and in vitro.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Review
- The effect of spermidine on autoimmunity and beta cell function in NOD mice.Scientific reports · 2022Article
- Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance.The Journal of clinical investigation · 2021Article
- Low-dose interleukin-2-loaded nanoparticle effect on NK and T-reg cell expression in experimentally induced type 1 diabetes mellitus.Przeglad gastroenterologiczny · 2021Article
- The Potential of Harnessing IL-2-Mediated Immunosuppression to Prevent Pathogenic B Cell Responses.Frontiers in immunology · 2021Review
- Effects of interleukin-2 in immunostimulation and immunosuppression.The Journal of experimental medicine · 2020Review
- Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways.Theranostics · 2020Article
- Effect of low dose IL-2 loaded chitosan nanoparticles on natural killer and regulatory T cell expression in experimentally induced autoimmune type 1 diabetes mellitus.Central-European journal of immunology · 2020Article
- Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers.Scientific reports · 2018Article
- Tumor Microenvironment-Induced Immunometabolic Reprogramming of Natural Killer Cells.Frontiers in immunology · 2018Review
- The contribution of interleukin-2 to effective wound healing.Experimental biology and medicine (Maywood, N.J.) · 2017Review
- The Expanding Role of Natural Killer Cells in Type 1 Diabetes and Immunotherapy.Current diabetes reports · 2016Review
- Loss of immune tolerance to IL-2 in type 1 diabetes.Nature communications · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Administration of low-dose interleukin-2 (IL-2) alone or combined with rapamycin (RAPA) prevents hyperglycemia in NOD mice. Also, low-dose IL-2 cures recent-onset type 1 diabetes (T1D) in NOD mice, partially by boosting pancreatic regulatory T cells (Treg cells). These approaches are currently being evaluated in humans. Our objective was to study the effect of higher IL-2 doses (250,000-500,000 IU daily) as well as low-dose IL-2 (25,000 IU daily) and RAPA (1 mg/kg daily) (RAPA/IL-2) combination. We show that, despite further boosting of Treg cells, high doses of IL-2 rapidly precipitated T1D in prediabetic female and male mice and increased myeloid cells in the pancreas. Also, we observed that RAPA counteracted IL-2 effects on Treg cells, failed to control IL-2-boosted NK cells, and broke IL-2-induced tolerance in a reversible way. Notably, the RAPA/IL-2 combination failure to cure T1D was associated with an unexpected deleterious effect on glucose homeostasis at multiple levels, including β-cell division, glucose tolerance, and liver glucose metabolism. Our data help to understand the therapeutic limitations of IL-2 alone or RAPA/IL-2 combination and could lead to the design of improved therapies for T1D.
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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.