Eomes transcription factor is required for the development and differentiation of invariant NKT cells

Commun Biol. 2019 Apr 29:2:150. doi: 10.1038/s42003-019-0389-3. eCollection 2019.

Abstract

Eomes regulates the differentiation of CD8+ T cells into effector and memory phases. However, its role in invariant (i)NKT cells remains unknown. Here, we show the impact of Eomes on iNKT cells in the thymus and peripheral tissue using conditional knockout (Eomes-cKO) mice. In the thymus, CD1d-tetramer+CD24+CD44-NK1.1-CD69+stage 0 iNKT cells express higher levels of Eomes than the other iNKT stages. We also found that Eomes regulates NKT1 cell differentiation predominantly. Interestingly, the expression of Eomes in the steady state is low, but can be upregulated after TCR stimulation. We also showed epigenetic changes in the Eomes locus after activation. In addition, vaccination of C57BL/6, but not Eomes-cKO mice with iNKT ligand-loaded dendritic cells generated KLRG1+iNKT cells in lung, characterized as effector memory phenotype by transcriptome profiling. Thus, Eomes regulates not only the differentiation of NKT1 cells in the thymus, but also their differentiation into memory-like KLRG1+iNKT cells in the periphery.

Keywords: Cytokines; Innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Cell Proliferation
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology*
  • Immunologic Memory / genetics*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Lung / cytology
  • Lung / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / cytology*
  • Natural Killer T-Cells / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Signal Transduction
  • T-Box Domain Proteins / deficiency
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transcriptome / immunology*

Substances

  • Antigens, CD
  • Eomes protein, mouse
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Immunologic
  • T-Box Domain Proteins