Cell reports · 2025
Eos plays a critical role in Treg homeostasis and modulates the function of recirculating thymic Tregs in the control of Treg development.
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Xie Xuan, Thornton Angela M, Tanwar Shalini, Korty Patricia, Wells Alexandria C, Segrist Elisha, Teijeiro Ana, Rivera Claudia A, Wei Danping, Chen Xi, Zhu Jinfang, Khleborodova Asya, Hill Tom, Markowitz Tovah E, Smelkinson Margery, Kabat Juraj, Veres Tibor, Schwartz Owen M, Otaizo-Carrasquero Francisco, Gardina Paul, Shamsaddini Amirhossein, Martens Craig, Cho Kyoungin, Lin Cheng-Chao, Khillan Jaspal S, Levin Yelena, Wu Ying, Shevach Ethan M
Аннотация
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 Treg precursors in the thymus by competing for IL-2 and depleting MHC II from thymic dendritic cells.