ArticleFrontiers in immunology2020
Defining the Threshold IL-2 Signal Required for Induction of Selective Treg Cell Responses Using Engineered IL-2 Muteins.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases.EBioMedicine · 2023Pooled it
- Effect of prior and first-line immunotherapy on baseline immune biomarkers and modulation of the tumor microenvironment in response to nivolumab and relatlimab combination therapy in patients with melanoma from RELATIVITY-020.Journal for immunotherapy of cancer · 2025Trial
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges.Frontiers in immunology · 2026Review
- Donor liver natural killer cells ameliorate liver allograft rejection via inducing apoptosis of alloreactive CD8Scientific reports · 2025Article
- The Role of Novel Immunomodulators in the Treatment of Autoimmune Hepatitis.Journal of clinical and translational hepatology · 2025Review
- Streptococcal pyrogenic exotoxin a induces regulatory T cells via TNF-α-TNFR2 signaling.Medical microbiology and immunology · 2025Article
- HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses.Cancer immunology, immunotherapy : CII · 2025Article
- Clinically approved immunotoxins targeting hematological cancers: "the best of both worlds".Frontiers in pharmacology · 2025Review
- Etiology and clinical significance of peripheral blood cytokines in geriatric patients with pulmonary infections.Frontiers in medicine · 2025Article
- Directed disruption of IL2 aggregation and receptor binding sites produces designer biologics with enhanced specificity and improved production capacity.Computational and structural biotechnology journal · 2025Article
- The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.JCI insight · 2024Article
- CD8-Targeted IL2 Unleashes Tumor-Specific Immunity in Human Cancer Tissue by Reviving the Dysfunctional T-cell Pool.Cancer discovery · 2024Article
- A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism.Communications medicine · 2024Article
- Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Regulatory T cells in dominant immunologic tolerance.The Journal of allergy and clinical immunology · 2024Review
- Potential Role of IL-37 in Atopic Dermatitis.Cells · 2023Review
- Multivalent, asymmetric IL-2-Fc fusions show enhanced selectivity for regulatory T cells.Science signaling · 2023Article
- Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies.Molecular cancer · 2023Review
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among all T and NK cell subsets, regulatory T (Treg) cells typically respond to the lowest concentrations of IL-2 due to elevated surface expression of the IL-2R alpha chain (IL2RA; CD25) and the high affinity IL-2 receptor (IL-2R) complex. This enhanced sensitivity forms the basis for low-dose (LD) IL-2 therapy for the treatment of inflammatory diseases, where efficacy correlates with increased Treg cell number and expression of functional markers. Despite strong preclinical support for this approach, moderate and variable clinical efficacy has raised concerns that adequate Treg selectivity still cannot be achieved with LD IL-2, and/or that doses are too low to stimulate effective Treg-mediated suppression within tissues. This has prompted development of IL-2 variants with greater Treg selectivity, achieved through attenuated affinity for the signaling chains of the IL-2R complex (IL2RB or CD122 and IL2RG or CD132) and, consequently, greater reliance on high CD25 levels for full receptor binding and signaling. While certain IL-2 variants have advanced to the clinic, it remains unknown if the full range of IL-2R signaling potency and Treg-selectivity observed with low concentrations of wildtype IL-2 can be sufficiently recapitulated with attenuated IL-2 muteins at high concentrations. Using a panel of engineered IL-2 muteins, we investigated how a range of IL-2R signaling intensity, benchmarked by the degree of STAT5 phosphorylation, relates to biologically relevant Treg cell responses such as proliferation, lineage and phenotypic marker expression, and suppressor function. Our results demonstrate that a surprisingly wide dynamic range of IL-2R signaling intensity leads to productive biological responses in Treg cells, with negligible STAT5 phosphorylation associating with nearly complete downstream effects such as Treg proliferation and suppressor activity. Furthermore, we show with both
Indexed as
Identifiers
What OpenQuestion holds
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.