Abstract
Objective. To summarize data on the role of interleukin-2 (IL-2) in the immunopathogenesis of rheumatoid arthritis (RA), evaluate the clinical experience with low-dose IL-2 (ldIL-2) therapy in RA, and determine the prospects for Treg-selective IL-2-based agents, including targeted delivery of IL-2 to regulatory T cells.
Material and methods. A targeted search of PubMed, ClinicalTrials.gov, and the Chinese Clinical Trial Registry (ChiCTR) was performed from database inception through 2026. The search terms included: rheumatoid arthritis, interleukin-2, low-dose IL-2, regulatory T cells, FOXP3, STAT5, CD25, IL2RA, IL-2 mutein, targeted delivery, TNFR2, CTLA-4, GARP/LRRC32, GITR, OX40, ICOS, CD39, CD73, CCR4, CCR8, and CXCR5.
Basic provisions. IL-2 promotes the survival and functional stability of Treg cells by stimulating FOXP3 expression. In RA, impaired immune regulation may manifest as a reduced number of Treg cells, diminished suppressive activity, or insufficient function within the inflammatory synovial microenvironment. Pilot studies of ldIL-2 have demonstrated an increase in circulating Treg cells; however, the available evidence remains insufficient to determine the durability of the clinical effect or the optimal treatment regimen. Promising approaches include engineered IL-2 variants with enhanced Treg selectivity, such as IL-2 muteins, pegylated and Fc-fused forms, bifunctional IL-2-containing proteins, and targeted-delivery agents directed at surface molecules preferentially expressed by Treg cells.
Conclusion. IL-2 is not currently a standard therapy for RA but represents a promising strategy for restoring immune tolerance. The most important near-term objectives are to demonstrate clinical efficacy, identify patient endotypes associated with treatment response, and improve the Treg selectivity of IL-2 delivery.
Keywords
Authors and affiliations
https://elibrary.ru/vjbqhm
O.V. Boiko, R.I. Mukhamedzyanova
Federal State Budgetary Educational Institution of Higher Education “Astrakhan State Medical University”
of the Ministry of Health of Russia, Bakinskaya St., 121, Astrakhan, 414000, Russian Federation
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