The polycomb repressive complex 2 governs life and death of peripheral T cells
- Author(s)
- Zhang, Y; Kinkel, S; Maksimovic, J; Bandala-Sanchez, E; Tanzer, MC; Naselli, G; Zhang, JG; Zhan, Y; Lew, AM; Silke, J; Oshlack, A; Blewitt, ME; Harrison, LC;
- Details
- Publication Year 2014-06-20,Volume 124,Issue #5,Page 737-749
- Journal Title
- Blood
- Publication Type
- Journal Article
- Abstract
- Differentiation of naive CD4+ T cells into effector (Th1, Th2 and Th17) and induced regulatory (iTreg) T cells requires lineage-specifying transcription factors and epigenetic modifications that allow appropriate repression or activation of gene transcription. The epigenetic silencing of cytokine genes is associated with the repressive H3K27 trimethylation mark, mediated by the Ezh2 or Ezh1 methyltransferase components of the polycomb repressive complex 2 (PRC2). Here we show that silencing of the Ifng, Gata3 and Il10 loci in naive CD4+ T cells is dependent on Ezh2. Naive CD4+ T cells lacking Ezh2 were epigenetically primed for overproduction of IFN-gamma in Th2 and iTreg and IL-10 in Th2 cells. In addition, deficiency of Ezh2 accelerated effector Th cell death via death receptor mediated-extrinsic and intrinsic apoptotic pathways, confirmed in vivo for Ezh2-null IFN-gamma-producing CD4+ and CD8+ T cells responding to Listeria monocytogenes infection. These findings demonstrate the key role of PRC2/Ezh2 in differentiation and survival of peripheral T cells and reveal potential immunotherapeutic targets.
- Publisher
- ASH
- Research Division(s)
- Immunology; Molecular Medicine; Cancer And Haematology; Cell Signalling And Cell Death
- Publisher's Version
- https://doi.org/10.1182/blood-2013-12-544106
- NHMRC Grants
- NHMRC/305500, NHMRC/1016647,
- Terms of Use/Rights Notice
- Copyright © 2014 American Society of Hematology
Creation Date: 2014-06-23 09:17:34
Last Modified: 2015-09-04 11:32:43