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: 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.