Format

Send to

Choose Destination
Nat Immunol. 2014 May;15(5):439-448. doi: 10.1038/ni.2864. Epub 2014 Mar 30.

CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2.

Author information

1
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
2
Division of Rheumatology, Medicine III, Medical University of Vienna, 1090 Vienna, Austria.
3
Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, 1030 Vienna, Austria.
4
Division of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria.
5
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
6
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
7
Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
8
Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, 4058 Basel, Switzerland and University of Basel, Faculty of Sciences, 4051 Basel, Switzerland.
#
Contributed equally

Erratum in

  • Nat Immunol. 2014 Sep;15(9):894. Goeschl, Lisa [corrected to Göschl, Lisa].

Abstract

Molecular mechanisms that maintain lineage integrity of helper T cells are largely unknown. Here we show histone deacetylases 1 and 2 (HDAC1 and HDAC2) as crucial regulators of this process. Loss of HDAC1 and HDAC2 during late T cell development led to the appearance of major histocompatibility complex (MHC) class II-selected CD4(+) helper T cells that expressed CD8-lineage genes such as Cd8a and Cd8b1. HDAC1 and HDAC2-deficient T helper type 0 (TH0) and TH1 cells further upregulated CD8-lineage genes and acquired a CD8(+) effector T cell program in a manner dependent on Runx-CBFβ complexes, whereas TH2 cells repressed features of the CD8(+) lineage independently of HDAC1 and HDAC2. These results demonstrate that HDAC1 and HDAC2 maintain integrity of the CD4 lineage by repressing Runx-CBFβ complexes that otherwise induce a CD8(+) effector T cell-like program in CD4(+) T cells.

PMID:
24681565
PMCID:
PMC4346201
DOI:
10.1038/ni.2864
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center