biostudies-literatureXie XIntramural NIH HHSNational Institute of Allergy and Infectious Diseases Division of Intramural ResearchNational Institutes of Health116838https://www.ebi.ac.uk/biostudies/studies/S-EPMC12869356biostudies-literatureUnknown45(1)Eos, a member of the Ikaros family of transcription factors, is expressed by T regulatory cells (Tregs) and has been postulated to play a role in Treg suppression and maintenance of Treg stability. We demonstrate that expression of Eos was limited to a subpopulation of thymus-derived, activated Tregs and is undetectable in resting or activated T conventional cells. Eos associates with Helios and Foxp3 and binds directly to the CD25 locus at a site identical to the Foxp3-binding site, thereby enhancing CD25 expression. Studies in heterozygous female mice demonstrate that Eos is critical for Treg survival and activation. Eos⁺ Tregs also represent the major population of recirculating thymic Tregs, in which Eos plays a critical role in regulating their migration and suppression of Cell reportsEos plays a critical role in Treg homeostasis and modulates the function of recirculating thymic Tregs in the control of Treg development.PMC12869356AI000959-20Z01 AI000959Hill TVeres TMarkowitz TEShamsaddini AKabat JLin CCSmelkinson MOtaizo-Carrasquero FWells ACGardina PShevach EMCho KRivera CAChen XSegrist EWu YXie XWei DTeijeiro AKhleborodova ASchwartz OMThornton AMKhillan JSTanwar SZhu JMartens CLevin YKorty PfalseEos plays a critical role in Treg homeostasis and modulates the function of recirculating thymic Tregs in the control of Treg development.Eos, a member of the Ikaros family of transcription factors, is expressed by T regulatory cells (Tregs) and has been postulated to play a role in Treg suppression and maintenance of Treg stability. We demonstrate that expression of Eos was limited to a subpopulation of thymus-derived, activated Tregs and is undetectable in resting or activated T conventional cells. Eos associates with Helios and Foxp3 and binds directly to the CD25 locus at a site identical to the Foxp3-binding site, thereby enhancing CD25 expression. Studies in heterozygous female mice demonstrate that Eos is critical for Treg survival and activation. Eos⁺ Tregs also represent the major population of recirculating thymic Tregs, in which Eos plays a critical role in regulating their migration and suppression of 2026-01-01T00:00:00Z2026 Jan2026-07-15T12:06:20.608Z2026-07-04T03:12:06.801ZS-EPMC128693564147462110.1016/j.celrep.2025.116838