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

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: XXXX‐XXXX] Mazzoni et al. and 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 towards 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 inflammed 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.

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