ArticleThe Journal of experimental medicine2026
Receptor-tethered orthogonal IL-2 enhances regulatory T cell therapy.
Article in The Journal of experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Cytokine-independent activation of STAT5 promotes the persistence and function of CD4Molecular therapy. Advances · 2026Article
- Next-Generation regulatory T cell therapies: Translational considerations for inflammatory bowel disease.Human immunology · 2026Review
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- Thirty years in, regulatory T cells are ready for medicine.Frontiers in immunology · 2026Review
- From rough to refined: Applying diamond standards to CAR Treg development.Molecular therapy. Methods & clinical development · 2025Article
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12 authors.
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Abstract
Regulatory T cell (Treg) therapy is an emerging platform for controlling immune overactivation. Persistence of infused Tregs is limited by insufficient IL-2, which is essential for Treg survival and function. IL-2 activates many immune cells, imposing a challenge for the selective provision of IL-2 to infused Tregs. In this study, we found that infusions of orthogonal (ortho) IL-2 failed to enhance Tregs expressing a corresponding orthoIL-2 receptor (IL-2R) in a mouse model of autoimmune diabetes. Engineering Tregs with an orthoIL-2 tethered to its receptor achieved selective autocrine signaling; increased CD25, CTLA-4, and Foxp3 expression; supported Treg persistence without exogenous IL-2 in vivo; and improved the efficacy of Treg prevention of autoimmune diabetes. Inserting the tethered orthoIL-2 construct into the Foxp3 locus enabled Treg-specific self-reinforced expression through the activation of the Foxp3 locus by increased IL-2 signaling. Together, these results illustrate a safe and effective cell-engineering solution for overcoming Tregs' dependency on exogenous IL-2, thereby achieving superior therapeutic efficacy.
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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.