Eos 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 Treg precursors in the thymus by competing for IL-2 and depleting MHC II from thymic dendritic cells.