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

Lookup NU author(s): Dr Arian Laurence



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Yang X-P, Jiang K, Hirahara K, Vahedi G, Afzali B, Sciume G, Bonelli M, Sun H-W, Jankovic D, Kanno Y, Sartorelli V, O'Shea JJ, Laurence A

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2015

Volume: 5

Online publication date: 19/06/2015

Acceptance date: 27/04/2015

Date deposited: 13/06/2018

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/srep10643

PubMed id: 26090605


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