ArticleJournal of autoimmunity2015
Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells.
Article in Journal of autoimmunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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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.
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Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation.Haematologica · 2017Trial
- 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
- Review
- Low-dose IL-2 Ameliorates Experimental Autoimmune Myasthenia Gravis in Rats by Restoring the CD4-positive Helper T-cell Balance Via the JAK/STAT5 Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Targeted regulatory T cell activation by site-specific PEGylated interleukin-2 mitigates autoimmune inflammation.Journal of translational autoimmunity · 2025Article
- Human precursor T follicular regulatory cells are primed for differentiation into mature Tfr and disrupted during severe infections.Science advances · 2025Article
- Targeting psoriatic inflammation with natural compounds: mechanistic insights and therapeutic promise.Inflammopharmacology · 2025Review
- The role of ubiquitin ligases in regulating immune cell functions.Frontiers in immunology · 2025Review
- Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression.Frontiers in immunology · 2024Article
- Multivalent, asymmetric IL-2-Fc fusions show enhanced selectivity for regulatory T cells.Science signaling · 2023Article
- Overcoming lung cancer immunotherapy resistance by combining nontoxic variants of IL-12 and IL-2.JCI insight · 2023Article
- Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies.Molecular cancer · 2023Review
- Unlocking the potential of Tregs: innovations in CAR technology.Frontiers in molecular biosciences · 2023Review
- Low-dose IL-2 reduces IL-21Nature communications · 2022Article
- Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity.Nature communications · 2022Article
- Gut microbiota shed new light on the management of immune-related adverse events.Thoracic cancer · 2022Review
- Selective activation and expansion of regulatory T cells using lipid encapsulated mRNA encoding a long-acting IL-2 mutein.Nature communications · 2022Article
- Regulatory T Cell Therapy of Graft-versus-Host Disease: Advances and Challenges.International journal of molecular sciences · 2021Review
- Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis.Digestive diseases and sciences · 2021Review
- Regulatory T Cells-Related Genes Are under DNA Methylation Influence.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Regulatory T cells (Tregs) expressing FOXP3 are essential for the maintenance of self-tolerance and are deficient in many common autoimmune diseases. Immune tolerance is maintained in part by IL-2 and deficiencies in the IL-2 pathway cause reduced Treg function and an increased risk of autoimmunity. Recent studies expanding Tregs in vivo with low-dose IL-2 achieved major clinical successes highlighting the potential to optimize this pleiotropic cytokine for inflammatory and autoimmune disease indications. Here we compare the clinically approved IL-2 molecule, Proleukin, with two engineered IL-2 molecules with long half-lives owing to their fusion in monovalent and bivalent stoichiometry to a non-FcRγ binding human IgG1. Using nonhuman primates, we demonstrate that single ultra-low doses of IL-2 fusion proteins induce a prolonged state of in vivo activation that increases Tregs for an extended period of time similar to multiple-dose Proleukin. One of the common pleiotropic effects of high dose IL-2 treatment, eosinophilia, is eliminated at doses of the IL-2 fusion proteins that greatly expand Tregs. The long half-lives of the IL-2 fusion proteins facilitated a detailed characterization of an IL-2 dose response driving Treg expansion that correlates with increasingly sustained, suprathreshold pSTAT5a induction and subsequent sustained increases in the expression of CD25, FOXP3 and Ki-67 with retention of Treg-specific epigenetic signatures at FOXP3 and CTLA4.
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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.