The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation

Immunity. 2015 Feb 17;42(2):227-238. doi: 10.1016/j.immuni.2015.01.007. Epub 2015 Feb 10.


Regulatory T cells (Treg cells) are required for immune homeostasis. Chromatin remodeling is essential for establishing diverse cellular identities, but how the epigenetic program in Treg cells is maintained throughout the dynamic activation process remains unclear. Here we have shown that CD28 co-stimulation, an extracellular cue intrinsically required for Treg cell maintenance, induced the chromatin-modifying enzyme, Ezh2. Treg-specific ablation of Ezh2 resulted in spontaneous autoimmunity with reduced Foxp3(+) cells in non-lymphoid tissues and impaired resolution of experimental autoimmune encephalomyelitis. Utilizing a model designed to selectively deplete wild-type Treg cells in adult mice co-populated with Ezh2-deficient Treg cells, Ezh2-deficient cells were destabilized and failed to prevent autoimmunity. After activation, the transcriptome of Ezh2-deficient Treg cells was disrupted, with altered expression of Treg cell lineage genes in a pattern similar to Foxp3-deficient Treg cells. These studies reveal a critical role for Ezh2 in the maintenance of Treg cell identity during cellular activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / genetics
  • Autoimmunity / immunology
  • CD28 Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Chromatin Assembly and Disassembly
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation
  • Heparin-binding EGF-like Growth Factor / genetics
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Lymphocyte Activation / immunology*
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / immunology*
  • Promoter Regions, Genetic / genetics
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*


  • CD28 Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • Polycomb Repressive Complex 2

Associated data

  • GEO/GSE58998