Abstract
Recent reports give insights into the role of the T-box transcription factors, T-bet and Eomesodermin (Eomes), in NK cell biology. In this mini-review, we recapitulate the initial reports that delineate T-bet and Eomes as master regulators of NK cell development, maturation, and function. We discuss how T-bet and Eomes expression is regulated during NK cell development and peripheral maturation. Furthermore, we summarize the current literature on the role of T-bet and Eomes in the transcriptional regulation of NK cell function and review possible effects of T-box transcription factor anomalies during aging, infection, cancer, and after hematopoietic stem cell transplantation. We discuss how the current data argue in favor of a model of T-bet and Eomes synergy in transcriptional regulation of NK cell function and identify T-box transcription factors as potential targets for therapeutic interventions.
Highlights
The phylogenetically conserved family of T-box transcription factors, which share T-box DNAbinding domains, is critically involved in developmental processes in vertebrates
We summarize the current knowledge about the role of T-box protein in T cells (T-bet) and Eomes in NK cell development, peripheral maturation, and function
Given their impact in NK cell development, peripheral maturation and function, alterations in T-bet and Eomes expression could account for NK cell abnormalities in pathological conditions in which NK cells exert an essential role, such as infections and cancer
Summary
The phylogenetically conserved family of T-box transcription factors, which share T-box DNAbinding domains, is critically involved in developmental processes in vertebrates. The bulk of mature murine [6, 8, 9] and human [10,11,12] NK cells express high levels of T-bet and Eomes, but until recently, their impact on NK cell function was not known. Other ontologically distinct tissue residing NK cell subsets have been identified in salivary glands, skin, and FIGURE 1 | T-bet and Eomes in murine NK cell development and peripheral maturation. Salivary gland [18] and uterine [17, 19,20,21] NK cells express high levels of Eomes and are T-bet-independent for their development and appear to be a more distinct NK cell lineage (Figure 1). These findings support a model in which T-bet and Eomes cooperatively regulate IFN-γ production in NK cells while T-bet seems to be the crucial regulator of their cytotoxic activity
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