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.

EZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion / Yang, Xiang Ping; Jiang, Kan; Hirahara, Kiyoshi; Vahedi, Golnaz; Afzali, Behdad; Sciume', Giuseppe; Bonelli, Michael; Sun, Hong Wei; Jankovic, Dragana; Kanno, Yuka; Sartorelli, Vittorio; O'Shea, John J.; Laurence, Arian. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 5:(2015). [10.1038/srep10643]

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

SCIUME', GIUSEPPE;
2015

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.
2015
Animals; Autoimmune Diseases; Cell Differentiation; Colitis; Cytokines; Enhancer of Zeste Homolog 2 Protein; Gene Expression Regulation; Mice; Mice, Knockout; Polycomb Repressive Complex 2; T-Lymphocytes, Regulatory; Multidisciplinary
01 Pubblicazione su rivista::01a Articolo in rivista
EZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion / Yang, Xiang Ping; Jiang, Kan; Hirahara, Kiyoshi; Vahedi, Golnaz; Afzali, Behdad; Sciume', Giuseppe; Bonelli, Michael; Sun, Hong Wei; Jankovic, Dragana; Kanno, Yuka; Sartorelli, Vittorio; O'Shea, John J.; Laurence, Arian. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 5:(2015). [10.1038/srep10643]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/954016
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