ArticleDiabetes2015
Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic mechanisms supports the use of low-dose IL-2 therapy in 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 129 papers, 1 of them a synthesis that pooled it.
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Who cites it
129 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.
- A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases.EBioMedicine · 2023Pooled it
- A randomized double-blind placebo-controlled trial of low-dose interleukin-2 in relapsing-remitting multiple sclerosis.Journal of neurology · 2023Trial
- 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
- Combination GLP-1RA and Low-Dose IL-2 Modulates Peripheral Immune Activation and Attenuates CNS Inflammatory Transcript Signatures In Vivo.International journal of molecular sciences · 2026Article
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Reducing Diabetic Ketoacidosis in Pediatric Type 1 Diabetes: The Impact of Screening Programs and Early Disease-Modifying Treatment.Journal of clinical medicine · 2026Review
- Synergistic immunomodulatory combinations induce robust human tolerogenic dendritic cells for antigen-specific regulatory T cell generation.The Journal of pharmacology and experimental therapeutics · 2026Article
- Preoperative inflammatory profile in chronic coronary syndrome reveals interleukin-2 as a promising biomarker for postoperative atrial fibrillation risk stratification.International journal of cardiology. Heart & vasculature · 2026Article
- T Helper Cells and Cytokine Networks in the Immunopathogenesis of Multiple Sclerosis.ImmunoTargets and therapy · 2026Review
- Dysregulation of homeostatic cytokine receptors drives prolonged T cell activation following acute SARS-CoV-2 infection in humans.Nature communications · 2025Article
- Advancing diabetic foot ulcer therapy: structure-activity relationship approaches for combating reactive oxygen species.Molecular biology reports · 2025Review
- From Bench to Clinic: Advances in Anti-Inflammatory Therapies for Atherosclerotic Coronary Artery Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- BLIMP-1 and CEACAM1 cooperatively regulate human Treg homeostasis and function to control xenogeneic GVHD.JCI insight · 2025Article
- Reprogramming of Different Cell Lineages into Functional β-Cell Substitutes.Cellular reprogramming · 2025Review
- Growth of human regulatory CD4iScience · 2025Article
- Oncolytic VSV-IL-2 has enhanced anticancer vaccination adjuvant abilities.Journal for immunotherapy of cancer · 2025Article
- Advances of oncolytic vaccinia viruses armed with interleukin in tumor therapy.Frontiers in oncology · 2025Review
- Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.Nature reviews. Endocrinology · 2025Review
- Unveiling the link between arsenic toxicity and diabetes: an in silico exploration into the role of transcription factors.Toxicological research · 2024Article
- Assessing the effectiveness of Interleukin-2 therapy in experimental type 1 diabetes.Endocrine · 2024Article
69 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low-dose interleukin-2 (IL-2) inhibited unwanted immune responses in several clinical settings and is currently being tested in patients with type 1 diabetes (T1D). Low-dose IL-2 selectively targets regulatory T cells (Tregs), but the mechanisms underlying this selectivity are poorly understood. We show that IL-2-dependent STAT5 activation in Tregs from healthy individuals and patients with T1D occurred at an ∼10-fold lower concentration of IL-2 than that required by T memory (TM) cells or by in vitro-activated T cells. This selective Treg responsiveness is explained by their higher expression of IL-2 receptor subunit α (IL-2Rα) and γ chain and also endogenous serine/threonine phosphatase protein phosphates 1 and/or 2A activity. Genome-wide profiling identified an IL-2-dependent transcriptome in human Tregs. Quantitative assessment of selected targets indicated that most were optimally activated by a 100-fold lower concentration of IL-2 in Tregs versus CD4(+) TM cells. Two such targets were selectively increased in Tregs from T1D patients undergoing low-dose IL-2 therapy. Thus, human Tregs possess an IL-2-dependent transcriptional amplification mechanism that widens their selective responses to low IL-2. Our findings support a model where low-dose IL-2 selectively activates Tregs to broadly induce their IL-2/IL-2R gene program and provide a molecular underpinning for low-dose IL-2 therapy to enhance Tregs for immune tolerance in 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.