Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory γδ T cell subsets

Nat Immunol. 2013 Oct;14(10):1093-1100. doi: 10.1038/ni.2702. Epub 2013 Sep 1.


Two distinct subsets of γδ T cells that produce interleukin 17 (IL-17) (CD27(-) γδ T cells) or interferon-γ (IFN-γ) (CD27(+) γδ T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-γ-producing or IL-17-producing γδ T cell subsets in vivo. We found that CD27(+) γδ T cells were committed to the expression of Ifng but not Il17, whereas CD27(-) γδ T cells displayed permissive chromatin configurations at loci encoding both cytokines and their regulatory transcription factors and differentiated into cells that produced both IL-17 and IFN-γ in a tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Histones / metabolism
  • Methylation
  • Mice
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Transcriptome*


  • Cytokines
  • Histones
  • Receptors, Antigen, T-Cell, gamma-delta

Associated data

  • GEO/GSE42098