ArticleSignal transduction and targeted therapy2023
Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity.
Article in Signal transduction and targeted therapy, 2023. 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.
- Soluble IL-2 receptor and memory Treg profiles differentiate early rheumatoid arthritis from undifferentiated arthritis at initial presentation.Frontiers in immunology · 2026Article
- Site-specific PEGylation of proteins: Insights into structural and functional changes.Acta pharmaceutica Sinica. B · 2025Review
- Aberrant Subsets of Regulatory T Cells and their Correlations with Serum IL-2 in Patients with Rheumatoid Arthritis.Inflammation · 2025Article
- Interleukin Networks in GVHD: Mechanistic Crosstalk, Therapeutic Targeting, and Emerging Paradigms.International journal of molecular sciences · 2025Review
- Engineered iron oxide nanoplatforms: reprogramming immunosuppressive niches for precision cancer theranostics.Molecular cancer · 2025Review
- Clinical applications of circulating tumor cells in metastasis and therapy.Journal of hematology & oncology · 2025Review
- Understanding Immune Dynamics in Liver Transplant Through Mathematical Modeling.Bulletin of mathematical biology · 2025Article
- Selectivity of bovine interleukin-2 mutein stimulation on bovine peripheral blood mononuclear cells.The Journal of veterinary medical science · 2025Article
- Reshape the Fates of Treg and CD8+T Cells Through IL-2Rα by Synergizing Divergent Receptor-Biased IL-2 PEGylates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- Mesothelin-Mediated Paclitaxel Phase-Shifted Nanodelivery System for Molecular Ultrasound Imaging and Targeted Therapy Potential in Ovarian Cancer.Current drug delivery · 2025Article
- Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.Frontiers in immunology · 2025Review
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- Biospecific Chemistry for Covalent Linking of Biomacromolecules.Chemical reviews · 2024Review
- Characterize direct protein interactions with enrichable, cleavable and latent bioreactive unnatural amino acids.Nature communications · 2024Article
- A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism.Communications medicine · 2024Article
- Chemical immunology: Recent advances in tool development and applications.Cell chemical biology · 2024Review
- Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- A humanized IL-2 mutein expands Tregs and prolongs transplant survival in preclinical models.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
26 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-2 (IL-2) is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells (Tregs) and effector cells, leading to paradoxical consequences. Here, we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine (FSY) into IL-2 for proximity-enabled covalent binding to IL-2Rα to selectively promote Treg activation. We found that FSY-bearing IL-2 variants, such as L72-FSY, covalently bound to IL-2Rα via sulfur-fluoride exchange when in proximity, resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells. Further assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation, as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3 (LAG-3) and enhanced expression of programmed cell death protein-1 (PD-1). Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease (GvHD) resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 treatment. The efficacy of L72-FSY was further improved by N-terminal PEGylation, which increased its circulatory retention for preferential and sustained effects. This proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies.
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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.