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

Nicole Boucheron, Roland Tschismarov, Lisa Goeschl, Mirjam A. Moser, Sabine Lagger, Shinya Sakaguchi, Mircea Winter, Florian Lenz, Dijana Vitko, Florian P. Breitwieser, Lena Müller, Hammad Hassan, Keiryn L. Bennett, Jacques Colinge, Wolfgang Schreiner, Takeshi Egawa, Ichiro Taniuchi, Patrick Matthias, Christian Seiser, Wilfried Ellmeier

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish
Pages (from-to)439-448
Number of pages10
JournalNature immunology
Volume15
Issue number5
DOIs
StatePublished - May 2014

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