Eomesodermin‐expressing type 1 regulatory (EOMES+Tr1)‐like T cells: Basic biology and role in immune‐mediated diseases

Abstract

AbstractType 1 regulatory (Tr1) T cells are currently defined all T cells with regulatory functions that lack FOXP3 expression and produce IL‐10. Tr1 cells are heterogeneous, and the different reported properties of Tr1‐cell populations have caused some confusion in the field. Moreover, understanding the role of Tr1 cells in immune‐mediated diseases has been hampered by the lack of a lineage‐defining transcription factor. Several independent studies indicated recently that the transcription factor Eomesodermin (EOMES) could act as a lineage‐defining transcription factor in a population of IL‐10 and IFN‐γ co‐producing Tr1‐like cells, since EOMES directly induces IFN‐γ and cytotoxicity, enhances IL‐10, and antagonizes alternative T‐cell fates. Here, we review the known properties of EOMES+Tr1‐like cells. They share several key characteristics with other Tr1 cells (i.e., “Tr1‐like”), namely high IL‐10 production, cytotoxicity, and suppressive capabilities. Notably, they also share some features with FOXP3+Tregs, like downregulation of IL‐7R and CD40L. In addition, they possess several unique, EOMES‐dependent features, that is, expression of GzmK and IFN‐γ, and downregulation of type‐17 cytokines. Published evidence indicates that EOMES+Tr1‐like cells play key roles in graft‐versus‐host disease, colitis, systemic autoimmunity and in tumors. Thus, EOMES+Tr1‐like cells are key players of the adaptive immune system that are involved in several different immune‐mediated diseases.