T-bet and Eomes govern differentiation and function of mouse and human NK cells and ILC1

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.

Keywords: Eomes; ILCs; NK cell differentiation; T-bet; T-box transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Communicable Diseases / immunology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Lymphocyte Subsets / cytology*
  • Lymphocyte Subsets / immunology
  • Mice
  • Neoplasms / immunology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*
  • Zinc Finger E-box Binding Homeobox 2 / metabolism


  • DNA-Binding Proteins
  • EOMES protein, human
  • Eomes protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Zinc Finger E-box Binding Homeobox 2