EOMESODERMIN-expressing type 1 regulatory (EOMES + Tr1)-like T-cells: basic biology and role in immune-mediated diseases.

Type 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 down-regulation of IL-7R and CD40L. In addition, they possess several uique, EOMES-dependent features, i.e. expression of GzmK and IFN-γ, and down-regulation 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 a novel key player of the adaptive immune system, that are involved in several different immune-mediated diseases. This article is protected by copyright. All rights reserved.