Format

Send to

Choose Destination
Sci Rep. 2015 Jun 19;5:10643. doi: 10.1038/srep10643.

EZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion.

Author information

1
1] Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China [2] Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch National Institutes of Arthritis, and Musculoskeletal and Skin Diseases National Institutes of Health, Bethesda, MD 20892, USA.
2
Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch National Institutes of Arthritis, and Musculoskeletal and Skin Diseases National Institutes of Health, Bethesda, MD 20892, USA.
3
1] Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch National Institutes of Arthritis, and Musculoskeletal and Skin Diseases National Institutes of Health, Bethesda, MD 20892, USA [2] MRC Centre for Transplantation, King's College London, UK.
4
Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1930, USA.
5
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases.
6
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1930, USA.
7
1] Northern Centre for cancer care, Freeman hospital, Newcastle upon tyne, UK [2] NDM Experimental medicine, John Radcliffe hospital, Oxford, UK.

Abstract

The roles of EZH2 in various subsets of CD4(+) T cells are controversial and its mechanisms of action are incompletely understood. FOXP3-positive Treg cells are a critical helper T cell subset, and dysregulation of Treg generation or function results in systemic autoimmunity. FOXP3 associates with EZH2 to mediate gene repression and suppressive function. Herein, we demonstrate that deletion of Ezh2 in CD4 T cells resulted in reduced numbers of Treg cells in vivo and differentiation in vitro and an increased proportion of memory CD4 T cells in part due to exaggerated production of effector cytokines. Furthermore, we found that both Ezh2-deficient Treg cells and T effector cells were functionally impaired in vivo: Tregs failed to constrain autoimmune colitis and T effector cells neither provided a protective response to T. gondii infection nor mediated autoimmune colitis. The dichotomous function of EZH2 in regulating differentiation and senescence in effector and regulatory T cells helps to explain the apparent existing contradictions in literature.

PMID:
26090605
PMCID:
PMC4473539
DOI:
10.1038/srep10643
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center