ArticleeLife2021
Calibration of cell-intrinsic interleukin-2 response thresholds guides design of a regulatory T cell biased agonist.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed.
- CD25 genetic ablation on lymphoid cell lines to obtain models of stimulation through the Interleukin-2 beta/gamma receptor.Scientific reports · 2026Article
- Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics.Science (New York, N.Y.) · 2026Article
- Perinatal hyperandrogenization and immune activation in rodents model subtypes of autism.Translational psychiatry · 2026Article
- T cell engagers control solid tumors through clonal replacement and IL2-driven effector differentiation of CD8 T cells.bioRxiv : the preprint server for biology · 2026Article
- Miniaturized IL-2/anti-IL-2 immunocytokines selectively activate and support theFrontiers in immunology · 2026Article
- Mathematical Modeling ofBioengineering (Basel, Switzerland) · 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
- Cytokine Couture: Designer IL2 Molecules for the Treatment of Disease.ImmunoTargets and therapy · 2025Review
- Article
- Endothelial Shear Stress Metrics Associate With Proinflammatory Pathways at the Culprit Site of Coronary Erosion.JACC. Basic to translational science · 2024Article
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
- A single-agent fusion of human IL-2 and anti-IL-2 antibody that selectively expands regulatory T cells.Communications biology · 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
- The Expression of Selected Cytokine Genes in the Livers of Young Castrated Bucks after Supplementation with a Mixture of DryAnimals : an open access journal from MDPI · 2023Article
- IL-2-driven CD8Trends in immunology · 2023Review
- Overcoming lung cancer immunotherapy resistance by combining nontoxic variants of IL-12 and IL-2.JCI insight · 2023Article
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
- Development and function of FOXP3+ regulators of immune responses.Clinical and experimental immunology · 2023Article
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Interleukin-2 is a pleiotropic cytokine that mediates both pro- and anti-inflammatory functions. Immune cells naturally differ in their sensitivity to IL-2 due to cell type and activation state-dependent expression of receptors and signaling pathway components. To probe differences in IL-2 signaling across cell types, we used structure-based design to create and profile a series of IL-2 variants with the capacity to titrate maximum signal strength in fine increments. One of these partial agonists, IL-2-REH, specifically expanded Foxp3+ regulatory T cells with reduced activity on CD8+ T cells due to cell type-intrinsic differences in IL-2 signaling. IL-2-REH elicited cell type-dependent differences in gene expression and provided mixed therapeutic results: showing benefit in the in vivo mouse dextran sulfate sodium (DSS) model of colitis, but no therapeutic efficacy in a transfer colitis model. Our findings show that cytokine partial agonists can be used to calibrate intrinsic differences in response thresholds across responding cell types to narrow pleiotropic actions, which may be generalizable to other cytokine and growth factor systems.
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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.