ENAGenomicsExperimental Immunology IFReC, Osaka universityhttps://www.ebi.ac.uk/ena/browser/view/PRJDB18080MammaliaOne strategy for antigen-specific immunosuppression is to convert antigen-specific conventional T cells (Tconvs) into Foxp3+ regulatory T cells (Tregs) as stably suppressive as naturally occurring Tregs (nTregs). To achieve the conversion in vitro in mice and humans, we induced high Foxp3 expression in antigen- and IL-2-stimulated Tconvs by CDK8/19 inhibition, and installed Treg-specific epigenetic changes in Treg signature genes, especially Foxp3, by depriving CD28 co-stimulation during the Treg induction. Repeating this process, with intermittent resting cultures solely with IL-2, enabled efficient conversion of naïve as well as effector/memory CD4+ Tconvs, including Th1, Th2 and Th17 cells, into Foxp3+ Tregs transcriptionally and epigenetically similar to nTregs. Tregs thus induced were indeed functionally and phenotypically stable in vivo and effectively suppressed inflammatory bowel disease and graft-versus-host disease in mouse models. Adoptive cell therapy with such effector/memory Tconv-derived, functionally stable, induced Tregs can be instrumental in antigen- and disease-specific treatment of immunological diseases.ENAfalseMammaliaIn vitro induction of antigen-specific and functionally stable Treg cells from effector/memory conventional T cells for adoptive cell therapy of immunological diseases2025-09-082025-09-08PRJDB1808040674