Expression of Eos is critical for T regulatory cell (Treg) survival and function

Abstract

Abstract Eos is a transcription factor belonging to the Ikaros transcription factor family and is preferentially expressed in Treg and activated T-conventional (T conv) cells. Our previous studies had shown that young mice with a global deletion of Eos did not appear to have defective Treg. To fully characterize the role of Eos in Treg function, we generated Eosfl/flx Foxp3Cre (Eos cKO) mice. Beginning at 3–4 months of age, both CD4+ and CD8+ T cells, as well as Treg in the Eos cKO mice expressed an activated/memory phenotype. The percentage of Tregs in the Eos cKO mice was higher than controls, suggesting that the Eos deficient Tregs were attempting to inhibit the activated immune response. H&E staining revealed severe lymphoid infiltration of lungs, kidneys, liver, small intestine, salivary glands of Eos cKO mice. The autoimmune state in the Eos cKO mice was characterized by enhanced levels of IFN-g production by CD4+ Foxp3− T cells, elevated percentages of T-follicular helper cells, and elevated levels of serum anti-nuclear antibodies. Tregs from Eos cKO mice failed to protect in the IBD transfer model and cKO mice also demonstrated enhanced susceptibility to EAE. Nevertheless, the in vitro suppressive function of Treg from cKO was normal. We determined the phenotype of Eos deficient Tregs under non-inflammatory conditions in heterozygous Eosfl/fl Foxp3cre/+ female mice. Although the thymic development of Eos deficient Tregs was not impaired, a marked reduction in Eos deficient Tregs was present in secondary lymphoid tissues indicating a defect in Treg survival in a competitive environment. We conclude that Eos is not required for the development of Tregs, but plays a critical role in controlling many, but not all, of the suppressive functions of Treg.