TY - JOUR
T1 - The Polycomb protein Ezh2 regulates differentiation and plasticity of CD4+ T helper Type 1 and type 2 cells
AU - Tumes, Damon J.
AU - Onodera, Atsushi
AU - Suzuki, Akane
AU - Shinoda, Kenta
AU - Endo, Yusuke
AU - Iwamura, Chiaki
AU - Hosokawa, Hiroyuki
AU - Koseki, Haruhiko
AU - Tokoyoda, Koji
AU - Suzuki, Yutaka
AU - Motohashi, Shinichiro
AU - Nakayama, Toshinori
N1 - Funding Information:
We thank K. Sugaya, H. Asou, M. Kato, and T. Ito for excellent technical assistance. We also thank J. O’Shea for active discussion and comments on the manuscript. This work was supported by the Global COE Program (Global Center for Education and Research in Immune System Regulation and Treatment) and by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) (Grants-in-Aid: for Scientific Research (B) #21390147, (C) #24592083, Young Scientists (B) #22790452, #23790522, #24790460, #24790461, #25860351, and #25860352, and MEXT KAKENHI Grant Number 221S0002), the Ministry of Health, Labour and Welfare, The Uehara Memorial Foundation, Princes Takamatsu Cancer Research Fund, and Takeda Science Foundation. D.J.T. was supported by a Japanese Society for the Promotion of Science postdoctoral fellowship (#2109747).
PY - 2013/11/14
Y1 - 2013/11/14
N2 - After antigen encounter by CD4+ Tcells, polarizing cytokines induce the expression of master regulators that control differentiation. Inactivation of the histone methyltransferase Ezh2 was found to specifically enhance T helper 1 (Th1) and Th2 cell differentiation and plasticity. Ezh2 directly bound and facilitated correct expression of Tbx21 and Gata3 in differentiating Th1 and Th2 cells, accompanied by substantial trimethylation at lysine 27 of histone 3 (H3K27me3). In addition, Ezh2 deficiency resulted in spontaneous generation of discrete IFN-γ and Th2 cytokine-producing populations in nonpolarizing cultures, and under these conditions IFN-γ expression was largely dependent on enhanced expression of the transcription factor Eomesodermin. Invivo, loss of Ezh2 caused increased pathology in a model of allergic asthma and resulted in progressive accumulation of memory phenotype Th2 cells. This study establishes a functional link between Ezh2 and transcriptional regulation of lineage-specifying genes in terminally differentiated CD4+ Tcells.
AB - After antigen encounter by CD4+ Tcells, polarizing cytokines induce the expression of master regulators that control differentiation. Inactivation of the histone methyltransferase Ezh2 was found to specifically enhance T helper 1 (Th1) and Th2 cell differentiation and plasticity. Ezh2 directly bound and facilitated correct expression of Tbx21 and Gata3 in differentiating Th1 and Th2 cells, accompanied by substantial trimethylation at lysine 27 of histone 3 (H3K27me3). In addition, Ezh2 deficiency resulted in spontaneous generation of discrete IFN-γ and Th2 cytokine-producing populations in nonpolarizing cultures, and under these conditions IFN-γ expression was largely dependent on enhanced expression of the transcription factor Eomesodermin. Invivo, loss of Ezh2 caused increased pathology in a model of allergic asthma and resulted in progressive accumulation of memory phenotype Th2 cells. This study establishes a functional link between Ezh2 and transcriptional regulation of lineage-specifying genes in terminally differentiated CD4+ Tcells.
UR - https://www.scopus.com/pages/publications/84887549060
U2 - 10.1016/j.immuni.2013.09.012
DO - 10.1016/j.immuni.2013.09.012
M3 - Article
C2 - 24238339
AN - SCOPUS:84887549060
SN - 1074-7613
VL - 39
SP - 819
EP - 832
JO - Immunity
JF - Immunity
IS - 5
ER -