@article{95011a9b31ae4e42abc60bb7eb7d04e4,
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 (T H 0) and T H 1 cells further upregulated CD8-lineage genes and acquired a CD8 + effector T cell program in a manner dependent on Runx-CBFβ complexes, whereas T H 2 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.",
author = "Nicole Boucheron and Roland Tschismarov and Lisa Goeschl and Moser, \{Mirjam A.\} and Sabine Lagger and Shinya Sakaguchi and Mircea Winter and Florian Lenz and Dijana Vitko and Breitwieser, \{Florian P.\} and Lena M{\"u}ller and Hammad Hassan and Bennett, \{Keiryn L.\} and Jacques Colinge and Wolfgang Schreiner and Takeshi Egawa and Ichiro Taniuchi and Patrick Matthias and Christian Seiser and Wilfried Ellmeier",
note = "Funding Information: We thank W. Glaser for performing the microarray experiments, D. Printz for cell sorting, C. Humer for help with immunoblot analysis, E. Pfeiffer for help with irradiation, R. Bosselut (US National Cancer Institute, National Institutes of Health (NIH)) for the anti–Th-POK antibody and J. Zhu (US National Institute of Allergy and Infectious Diseases, NIH) for the GATA-3 vector. This study was funded by the Vienna Science and Technology Fund (WWTF) through project LS09-031 (to W.E. and C.S.). This work in the laboratory of W.E. was also supported by the Austrian Science Fund (FWF) and MedUni Vienna doctoral program (DK W1212) “Inflammation and Immunity” and by FWF projects (P19930, P23641 and I00698). The work in the laboratory of C.S. was supported by the FWF (P25807 and DKplus W1220) and the Genome Research in Austria project “Epigenetic Regulation of Cell Fate Decisions” (Federal Ministry of Science, Research and Economy, BMWFW). N.B. and S.S. are funded by the FWF (P24265 and P23669, respectively). L.G. has been supported from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115142 (BTCure), resources of which are composed of financial contribution from the FP7 of the European Union and the European Federation of Pharmaceutical Industries and Associations companies{\textquoteright} in kind contribution. T.E. is supported by NIH grant AI097244.",
year = "2014",
month = may,
doi = "10.1038/ni.2864",
language = "English",
volume = "15",
pages = "439--448",
journal = "Nature immunology",
issn = "1529-2908",
number = "5",
}