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/fwnqef
A.O. Solovieva(1), M.L. Filipenko(2), M.A. Korolev(1)
1Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics,
Siberian Branch of Russian Academy of Sciences, Arbuzova St., 6, Novosibirsk, 630117, Russian Federation; 2D.G. Knorre Institute
of Chemical Biology and Fundamental Medicine, Akademika Lavrentyeva Ave., 8, Novosibirsk, 630090, Russian Federation
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