The role of Eomes in human CD4 T cell differentiation: A question of context

Abstract

Eomesodermin (Eomes) is a transcription factor (TF) of the T-box family closely related to T-bet known for its role in CD8 T cell and natural killer cell differentiation. However, the role of Eomes in CD4 T-cell differentiation is less well appreciated. In this issue of the European Journal of Immunology[Eur. J. Immunol. 2019. 49: 79-95] Mazzoni et al. and [Eur. J. Immunol. 2019. 49: 96-111] Gruarin et al. studied the role of Eomes in human CD4 T-cell differentiation. Mazzoni et al. showed that Eomes plays a key role in helper T cell (Th) plasticity by favoring the phenotype shift of Th17 cells toward non-classic Th1 cells; while Gruarin et al. proposed Eomes as a lineage-defining TF for human IL-10 and IFN-γ co-producing regulatory T-cells (Tr1 cells). Both studies show that Eomes drives IFN-γ secretion and stamps a "cytotoxic" signature, while it also represses Th17 features. However, additional signals including the cytokine milieu may further influence the fate of Eomes + CD4 T cells. A common feature of Eomes + CD4 T cells appears to be their accumulation in inflamed tissues in patients with chronic inflammatory disorders. Whether Eomes favors expression of the proinflammatory cytokines or on the contrary, promotes the anti-inflammatory cytokines, remains a matter of debate.Keywords: EOMES r CD4 T cells r Regulatory T cells r Th1 r Th17 See accompanying articles by Mazzoni et al. and Gruarin et al.CD4 T cells can adopt different functional fates depending on the set of transcription factors (TF) they express, these TF being induced by various polarizing cytokines. Th1, Th2 and Th17 helper lineages are defined by expression of T-bet, Gata-3 and RORγt expression, respectively. Helper CD4 T cell subsets are also known to be highly plastic, especially the Th17 type. Th1 cells can derive directly from naïve CD4 T cells or from differentiated Th17 cells.

Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma

“…Previous studies have suggested that EOMES and RUNX3 contribute to the development and homeostasis of effector and memory T cells as well as NK cell differentiation. [40][41][42] Nevertheless, the role of XBP1 in regulating cytotoxic lymphocytes is less well understood, [43][44][45] and the effects of these regulators in immune responses have not been addressed in NPC. To validate the SCENIC results, we isolated CD8 + T cells and NK cells from the NPC tissue samples by flow cytometry (FACS), and identified a significantly higher percentage of cytotoxic GZMB + or perforin + phenotypes in the EOMES + , RUNX3 + , and XBP1 + CD8 + T cells and NK cells (Supplementary information, Fig.…”

Mycobacterium tuberculosis-specific CD4 T cells expressing CD153 inversely associate with bacterial load and disease severity in human tuberculosis

“…To better understand the specific phenotypic attributes of polyfunctional Mtb300-specific CD4 T cells expressing CD153, we compared the expression of CD27 (memory marker), HLA-DR (activation marker), KLRG1 (coinhibitory molecule), 14 and Eomes (Transcription factor) 15 in CD153+ IFNγ+ TNFα+ IL-2+ and CD153− IFNγ+ TNFα+ IL-2+ Mtb300-specific CD4 T cells in our four study groups (Fig. 5a).…”

EOMES and IL-10 regulate anti-tumor activity of PD-1+CD4+T-cells in B-cell Non-Hodgkin lymphoma

“…In cooperation with other factors like PR domain zinc finger protein 1 (BLIMP1), EOMES is a driver of IL-10 production in T R 1 T-cells in mice (7) as well as humans (8). Whether EOMES only promotes Il10 expression by T R 1 cells or is a lineage-defining transcription factor is still unclear (35).…”