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

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

Author information

1
Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
3
Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Innovative Genomics Initiative (IGI), University of California, Berkeley, CA 94720, USA.
4
Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jeff.bluestone@ucsf.edu.

Abstract

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.

PMID:
25680271
PMCID:
PMC4347854
DOI:
10.1016/j.immuni.2015.01.007
[Indexed for MEDLINE]
Free PMC Article

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