Eos plays a critical role in the function of recirculating thymic T regulatory cells (Tregs) 2114

Description Eos, a member of the Ikaros family, is highly expressed in Helios+ Tregs. Mice with a selective deficiency of Eos in Tregs develop autoimmune disease. Eos is co-localized with Helios and directly interacts with Helios. Eos expression can be induced on conventional T cells in vitro in a TCR, IL-2 and TGFb-dependent manner. Eos is not induced during Treg induction following oral tolerance, but under inflammatory conditions, Eos expression is unregulated on pTregs. The percentage of Eos+ Tregs rapidly increases with age during first 3 weeks of life and then increases slowly thereafter. In thymus, Eos expression is correlated with recirculating Treg markers. Studies in parabiotic mice demonstrate Tregs migrated back to thymus are predominantly Eos+. RNA sequencing of thymic Tregs shows Eos+ Tregs are enriched for GPCR related pathways and reduced for extracellular matrix related pathways compared to Eos- Tregs, suggesting different migration capacities. Deletion of Eos results in decreased CD25 expression and IL-2 responsiveness in recirculating thymic Tregs, but increased generation of Tregs. In vitro culture of Treg precursors with Eos deficient recirculating Treg in the presence of IL-2 results in increased generation of Tregs compared to co-culture with WT recirculating Tregs. Taken together, Eos plays an important role in recirculating thymic Tregs in regulating Treg precursors by IL-2 deprivation. Funding Sources This work was supported by Division of Intramural Research (DIR), NIAID, NIH.