EZH2 is Crucial for Both Differentiation of Regulatory T Cells and T Effector Cell Expansion

Overview

Journal Sci Rep

Specialty Science

Date 2015 Jun 20

PMID 26090605

Citations 84

Authors

Xiang-Ping Yang

Kan Jiang

Kiyoshi Hirahara

Golnaz Vahedi

Behdad Afzali

Giuseppe Sciume

Michael Bonelli

Hong-Wei Sun

Dragana Jankovic

Yuka Kanno

Vittorio Sartorelli

John J OShea

Arian Laurence

Affiliations

Soon will be listed here.

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.

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