CD4+ T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2.
- Resource Type
- Article
- Authors
- Boucheron, Nicole; Tschismarov, Roland; Goeschl, Lisa; Moser, Mirjam A; Lagger, Sabine; Sakaguchi, Shinya; Winter, Mircea; Lenz, Florian; Vitko, Dijana; Breitwieser, Florian P; Müller, Lena; Hassan, Hammad; Bennett, Keiryn L; Colinge, Jacques; Schreiner, Wolfgang; Egawa, Takeshi; Taniuchi, Ichiro; Matthias, Patrick; Seiser, Christian; Ellmeier, Wilfried
- Source
- Nature Immunology. May2014, Vol. 15 Issue 5, p439-448. 10p.
- Subject
- *HISTONE deacetylase regulation
*CD4 antigen
*T cells
*T helper cells
*MAJOR histocompatibility complex
*CD8 antigen
*RUNX proteins
- Language
- ISSN
- 1529-2908
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. [ABSTRACT FROM AUTHOR]