Eos is a critical transcription factor for T regulatory cell (Treg) function

Abstract

Abstract Eos is a member of the Ikaros transcription factor family and is highly expressed in Tregs. Mice with a selective deficiency of Eos in Treg develop systemic or organ-specific autoimmune disease at at a young age. We have generated a specific anti-Eos monoclonal antibody. The percentage of Tregs expressing Eos rapidly increases with aging from almost 0% at birth to 30~50% of thymic Tregs and 35~60% of splenic Tregs at 3 weeks of life and then remains stable. Eos is expressed at very low levels on induced Tregs, conventional CD4 +T cells and CD8 +T cells in vivo or in vitro. In the thymus, Eos is only expressed on CD73 +CCR6 +CXCR4 +Tregs, which suggests that Eos +thymic Tregs represent peripheral Tregs that have recirculated to the thymus. In thymus, Eos expression on Tregs is also highly correlated with CXCR4 and CCR6. Using these markers, we sorted Eos +and Eos −Tregs and in vitro expanded them using anti-CD3/CD28 beads and IL-2; Eos expression remained stable. Using immunofluorescence microscopy, we have found that Eos is highly co-localized with Helios, another Ikaros family member and HDAC1, but not other Ikaros family members including Ikaros or Aiolos, suggesting that Eos and Helios may form heterodimers and together with HDAC1 collaborate in Treg function. Nevertheless, expression of Eos is independent of Helios and vice versa, as Treg from Helios deficient mice express normal or elevated levels of Eos, and Treg from Eos deficient mice express normal levels of Helios. Taken together, these strongly suggest that Eos plays a related, but distinct role, from Helios in Treg function. This work was supported by Division of Intramural Research (DIR), NIAID, NIH.