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Review
. 2023 May;53(5):e2149775.
doi: 10.1002/eji.202149775. Epub 2023 Mar 17.

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

Jens Geginat  1   2 , Chiara Vasco  1 , Paola Gruarin  1 , Raoul Bonnal  1   3 , Grazisa Rossetti  1   3 , Ylenia Silvestri  1 , Elena Carelli  1 , Nadia Pulvirenti  1 , Morena Scantamburlo  1 , Giorgia Moschetti  1 , Francesca Clemente  1 , Fabio Grassi  1   4 , Silvia Monticelli  4   5 , Massimiliano Pagani  1   3 , Sergio Abrignani  1   2
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Free article
Review

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

Jens Geginat et al. Eur J Immunol. 2023 May.
Free article

Abstract

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 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.

Keywords: Cytotoxicity; Eomesodermin; IL-10; Regulatory T cells; Type 1 regulatory T cells.

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References

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