ArticleDiabetes2020
Persistent IL-2 Receptor Signaling by IL-2/CD25 Fusion Protein Controls Diabetes in NOD Mice by Multiple Mechanisms.
Article in Diabetes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- IL-2/CD25 acts within the tumor microenvironment to reprogram tumor-specific cytotoxic CD8Journal for immunotherapy of cancer · 2026Article
- The transcription factor SREBP2 supports the activation and homeostasis of CD4+ Foxp3+ regulatory T cells.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Article
- Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.Oncoimmunology · 2025Review
- Role of Interleukins in Type 1 and Type 2 Diabetes.Diagnostics (Basel, Switzerland) · 2025Review
- Pharmacotherapeutic strategies to promote regulatory T cell function in autoimmunity.Current opinion in immunology · 2025Review
- Gluten-Free Diet Induces Small-Scale Changes Across Multiple T-Cell Subsets in NOD Mice.European journal of immunology · 2025Article
- Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets.iScience · 2024Article
- Changes in CD4+CD25HIGH T cells and TGFβ1 levels in different stages of adult-onset type 1 diabetes.Journal of medical biochemistry · 2024Article
- Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024Review
- Regulatory T Cell Dysfunction in Autoimmune Diseases.International journal of molecular sciences · 2024Review
- Refined protocol for newly onset identification in non-obese diabetic mice: an animal-friendly, cost-effective, and efficient alternative.Laboratory animal research · 2024Article
- Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?Molecular and cellular pediatrics · 2024Review
- Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer.Immunity · 2024Review
- Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
- "IL-2 immunotherapy for targeting regulatory T cells in autoimmunity".Genes and immunity · 2023Review
- Robust IL-2-dependent antitumor immunotherapy requires targeting the high-affinity IL-2R on tumor-specific CD8Journal for immunotherapy of cancer · 2023Article
- Immunotherapy With Low-Dose IL-2/CD25 Prevents β-Cell Dysfunction and Dysglycemia in Prediabetic NOD Mice.Diabetes · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Low-dose interleukin-2 (IL-2) represents a new therapeutic approach to regulate immune homeostasis to promote immune tolerance in patients with autoimmune diseases, including type 1 diabetes. We have developed a new IL-2-based biologic, an IL-2/CD25 fusion protein, with greatly improved pharmacokinetics and pharmacodynamics when compared with recombinant IL-2 to enhance this type of immunotherapy. In this study, we show that low-dose mouse IL-2/CD25 (mIL-2/CD25), but not an equivalent amount of IL-2, prevents the onset of diabetes in NOD mice and controls diabetes in hyperglycemic mice. mIL-2/CD25 acts not only to expand regulatory T cells (Tregs) but also to increase their activation and migration into lymphoid tissues and the pancreas. Lower incidence of diabetes is associated with increased serum levels of IL-10, a cytokine readily produced by activated Tregs. These effects likely act in concert to lower islet inflammation while increasing Tregs in the remaining inflamed islets. mIL-2/CD25 treatment is also associated with lower anti-insulin autoantibody levels in part by inhibition of T follicular helper cells. Thus, long-acting mIL-2/CD25 represents an improved IL-2 analog that persistently elevates Tregs to maintain a favorable Treg/effector T cell ratio that limits diabetes by expansion of activated Tregs that readily migrate into lymphoid tissues and the pancreas while inhibiting autoantibodies.
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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.