CIRI, Centre International de Recherche en Infectiologie-International Center for Infectiology Research, Inserm, U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS, UMR5308, Lyon, France.
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Eur J Immunol. 2018 May;48(5):738-750. doi: 10.1002/eji.201747299. Epub 2018 Feb 28.
T-bet and Eomes are T-box transcription factors that drive the differentiation and function of cytotoxic lymphocytes such as NK cells. Their DNA-binding domains are highly similar, suggesting redundant transcriptional activity. However, while these transcription factors have different patterns of expression, the phenotype of loss-of-function mouse models suggests that they play distinct roles in the development of NK cells and other innate lymphoid cells (ILCs). Recent technological advances using reporter mice and conditional knockouts were fundamental in defining the regulation and function of these factors at steady state and during pathological conditions such as various types of cancer or infection. Here, we review these recent developments, focusing on NK cells as prototypical cytotoxic lymphocytes and their development, and also discuss parallels between NK cells and T cells. We also examine the role of T-bet and Eomes in human NK cells and ILC1s. Considering divergent findings on mouse and human ILC1s, we propose that NK cells are defined by coexpression of T-bet and Eomes, while ILC1s express only one of these factors, either T-bet or Eomes, depending on the tissue or the species.
T-bet 和 Eomes 是 T 盒转录因子，它们驱动 NK 细胞等细胞毒性淋巴细胞的分化和功能。它们的 DNA 结合域高度相似，表明转录活性存在冗余。然而，尽管这些转录因子的表达模式不同，但功能丧失型小鼠模型的表型表明它们在 NK 细胞和其他固有淋巴细胞（ILC）的发育中发挥着不同的作用。最近使用报告小鼠和条件性敲除的技术进步，对于在稳态和各种类型的癌症或感染等病理条件下，定义这些因子的调控和功能至关重要。在这里，我们回顾这些最新的进展，重点关注 NK 细胞作为典型的细胞毒性淋巴细胞及其发育，并讨论 NK 细胞与 T 细胞之间的平行关系。我们还研究了 T-bet 和 Eomes 在人 NK 细胞和 ILC1 中的作用。考虑到在小鼠和人类 ILC1 中发现的分歧结果，我们提出 NK 细胞的定义是同时表达 T-bet 和 Eomes，而 ILC1 则根据组织或物种，只表达这两个因子中的一个，即 T-bet 或 Eomes。
