title: CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2.
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.
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Boucheron
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Tschismarov
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.|Division of Rheumatology, Medicine III, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Goeschl
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, 1030 Vienna, Austria.
authors.forename: Mirjam A
authors.initials: MA
authors.lastname: Moser
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, 1030 Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Lagger
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakaguchi
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, 1030 Vienna, Austria.
authors.forename: Mircea
authors.initials: M
authors.lastname: Winter
authors.affiliation: Division of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Lenz
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors.forename: Dijana
authors.initials: D
authors.lastname: Vitko
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors.forename: Florian P
authors.initials: FP
authors.lastname: Breitwieser
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Lena
authors.initials: L
authors.lastname: Müller
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Hammad
authors.initials: H
authors.lastname: Hassan
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors.forename: Keiryn L
authors.initials: KL
authors.lastname: Bennett
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors.forename: Jacques
authors.initials: J
authors.lastname: Colinge
authors.affiliation: Division of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schreiner
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Egawa
authors.affiliation: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, 4058 Basel, Switzerland and University of Basel, Faculty of Sciences, 4051 Basel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, 1030 Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Seiser
authors.affiliation: Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Ellmeier
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C493693:Cbfb protein, mouse; D050657:Core Binding Factor alpha Subunits; D050658:Core Binding Factor beta Subunit; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2