Eos Is Redundant for Regulatory T Cell Function but Plays an Important Role in IL-2 and Th17 Production by CD4+ Conventional T Cells

Abstract

Eos is a transcription factor that belongs to the Ikaros family of transcription factors. Eos has been reported to be a T regulatory cell (Treg) signature gene, to play a critical role in Treg suppressor functions, and to maintain Treg stability. We have utilized mice with a global deficiency of Eos to re-examine the role of Eos expression in both Treg and T conventional (Tconv) cells. Treg from Eos deficient (Eos−/−) mice developed normally, displayed a normal Treg phenotype, and exhibited normal suppressor function in vitro. Eos−/− Treg were as effective as Treg from wild type (WT) mice in suppression of inflammation in a model of inflammatory bowel disease. Bone marrow (BM) from Eos−/− mice was as effective as BM from WT mice in controlling T cell activation when used to reconstitute immunodeficient mice in the presence of Scurfy fetal liver cells. Surprisingly, Eos was expressed in activated Tconv cells and was required for IL-2 production, CD25 expression and proliferation in vitro by CD4+ Tconv cells. Eos−/− mice developed more severe Experimental Autoimmune Encephalomyelitis than WT mice, displayed increased numbers of effector T cells in the periphery and CNS, and amplified IL-17 production. In conclusion, our studies are not consistent with a role for Eos in Treg development and function, but demonstrate that Eos plays an important role in the activation and differentiation of Tconv cells.

Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them?

“…Of note, global deletion of Eos in mice does not affect the function or phenotype of T regs in vivo and in vitro, but does result in the development of more severe EAE. This observation was attributed to the function of Eos in T eff populations (129). …”

The neutrophil antimicrobial peptide cathelicidin promotes Th17 differentiation

“…Following cathelicidin exposure, we noted a consistent, significant decrease in the expression of a number of genes which suppress the induction or conversion of cells into the Th17 subset [68][69][70][71] including Socs3, Stat1, Irf8, Bcl3 and Ikzf4 (Fig. 3A, B).…”

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“…Eos (encoded by Ikzf4), another member of the Ikaros family, is also critical in Treg cell biology. Eos is highly expressed by Treg cells, although in vitro stimulated Tconv cells can express substantial levels of the protein, and physically interacts with Foxp3 to help mediate Foxp3-mediated gene repression in Treg cells [57,58]. Eos is mainly expendable for Tconv cell function in vivo [58].…”

“…Eos is highly expressed by Treg cells, although in vitro stimulated Tconv cells can express substantial levels of the protein, and physically interacts with Foxp3 to help mediate Foxp3-mediated gene repression in Treg cells [57,58]. Eos is mainly expendable for Tconv cell function in vivo [58]. In contrast, Ikzf4 knock-down or knock-out drives loss of numerous Treg-specific genes and expression of Tconv-associated genes [57].…”