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Improvement of Treg Selectivity and Stability for Diabetes Mellitus Type 1 Treatment: Complex Approach for

Andrei A Riabinin1, Dmitry D Zhdanov1,2,3, Varvara G Blinova1,2

  • 1Koltzov Institute of Developmental Biology of Russian Academy of Sciences, 26 Vavilov Street, Moscow 119334, Russia.

Cells
|November 26, 2025
PubMed

The adoptive transfer of Tregs is a promising immunotherapeutic strategy for type 1 diabetes mellitus (T1D). A key focus in this field is the creation of antigen-specific CAR-Tregs targeted against pancreatic islet antigens. However, the efficacy of such therapies is potentially limited by the instability of the Treg phenotype in the inflammatory conditions of T1D. This review discusses molecular approaches to overcome this limitation. These include the genetic engineering of cytokine signaling pathways (IL2, IL33/ST2, and IL35) and the cAMP cascade, the management of FOXP3 splicing to ensure stable expression of concrete splice variants, and the use of epigenetic mechanisms to promote a durable Treg identity.

Keywords:
alternative splicingdiabetes mellitus type 1epigenetic modificationsgenetic modificationsregulatory T cells

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