ArticleDiabetes2015
Natural Variation in Interleukin-2 Sensitivity Influences Regulatory T-Cell Frequency and Function in Individuals With Long-standing Type 1 Diabetes.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 58 citations in OpenAlex.
- Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.PLoS medicine · 2016Trial
- Genetic association stratified by HLA-DR3 and HLA-DR4 status reveals heterogeneity in pathways of progression to type 1 diabetes.Diabetologia · 2026Article
- Article
- Adapting CAR-T and CAR-Treg cancer therapies for autoimmunity: innovations and challenges.Frontiers in immunology · 2026Review
- Tregs in pregnancy with type 1 diabetes mellitus: pilot study.Revista da Associacao Medica Brasileira (1992) · 2025Article
- Regulatory T cell dysfunction and immunotherapeutic breakthroughs in type 1 diabetes.Frontiers in endocrinology · 2025Review
- The role of ubiquitin ligases in regulating immune cell functions.Frontiers in immunology · 2025Review
- The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.JCI insight · 2024Article
- Physiological and pathogenic T cell autoreactivity converge in type 1 diabetes.Nature communications · 2024Article
- Review
- Genetic engineering of regulatory T cells for treatment of autoimmune disorders including type 1 diabetes.Diabetologia · 2024Review
- Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?Molecular and cellular pediatrics · 2024Review
- GNTI-122: an autologous antigen-specific engineered Treg cell therapy for type 1 diabetes.JCI insight · 2024Article
- Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection.Frontiers in endocrinology · 2024Review
- Insulin-like Growth Factor-1 Synergizes with IL-2 to Induce Homeostatic Proliferation of Regulatory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Allogenic Umbilical Cord-Derived Mesenchymal Stromal Cells Sustain Long-Term Therapeutic Efficacy Compared With Low-Dose Interleukin-2 in Systemic Lupus Erythematosus.Stem cells translational medicine · 2023Article
- Development and function of FOXP3+ regulators of immune responses.Clinical and experimental immunology · 2023Article
- IL-2-based approaches to Treg enhancement.Clinical and experimental immunology · 2023Review
- Modeling human T1D-associated autoimmune processes.Molecular metabolism · 2022Review
- Genetic basis of defects in immune tolerance underlying the development of autoimmunity.Frontiers in immunology · 2022Review
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Authors and funding
13 authors at 3 institutions in 4 countries.
Funding
Abstract
Defective immune homeostasis in the balance between FOXP3+ regulatory T cells (Tregs) and effector T cells is a likely contributing factor in the loss of self-tolerance observed in type 1 diabetes (T1D). Given the importance of interleukin-2 (IL-2) signaling in the generation and function of Tregs, observations that polymorphisms in genes in the IL-2 pathway associate with T1D and that some individuals with T1D exhibit reduced IL-2 signaling indicate that impairment of this pathway may play a role in Treg dysfunction and the pathogenesis of T1D. Here, we have examined IL-2 sensitivity in CD4+ T-cell subsets in 70 individuals with long-standing T1D, allowing us to investigate the effect of low IL-2 sensitivity on Treg frequency and function. IL-2 responsiveness, measured by STAT5a phosphorylation, was a very stable phenotype within individuals but exhibited considerable interindividual variation and was influenced by T1D-associated PTPN2 gene polymorphisms. Tregs from individuals with lower IL-2 signaling were reduced in frequency, were less able to maintain expression of FOXP3 under limiting concentrations of IL-2, and displayed reduced suppressor function. These results suggest that reduced IL-2 signaling may be used to identify patients with the highest Treg dysfunction and who may benefit most from IL-2 immunotherapy.
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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.