IMMUNOLOGY2025™ Conference Recordings-Induction of regulatory T cells for immune tolerance

Video Transcription

Video Summary

The speaker discusses how to generate antigen-specific regulatory T cells (Treg) from effector-memory T cells for treating autoimmune and other immune-mediated diseases. Natural Treg are characterized by FOXP3, CTLA-4, and high-affinity IL-2 receptor expression, and their stability depends not only on transcription factors but also on a Treg-specific epigenetic program, including DNA demethylation and chromatin remodeling. In contrast, in vitro-induced Treg often lose FOXP3 and suppressive function after transfer because they lack this stable epigenome.<br /><br />The talk focuses on converting conventional or memory T cells into “stable functional induced Treg” (SF-iTreg) by inducing both FOXP3 expression and Treg-like epigenetic changes. The speaker describes CRISPR screening and chemical screening approaches, identifying factors such as CDK8/19 inhibition that promote FOXP3 induction. Importantly, removing CD28 co-stimulation helps generate Treg with stronger Treg-type DNA demethylation and better stability.<br /><br />These SF-iTreg can suppress disease in animal models, including desmoglein-3-specific pemphigus vulgaris, where they prevent autoantibody production and skin blistering. Similar strategies may apply to SLE, Crohn’s disease, and transplantation, especially when the target antigen is unknown or multiple antigens are involved.

Keywords

regulatory T cells

FOXP3

epigenetic stability

CD28 co-stimulation

CRISPR screening

autoimmune disease therapy

antigen-specific Treg