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-CBFbeta 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-CBFbeta complexes that otherwise induce a CD8(+) effector T cell-like program in CD4(+) T cells.
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https://hal.umontpellier.fr/hal-02168080
Contributeur : Cécile Nowak <>
Soumis le : vendredi 28 juin 2019 - 13:50:56
Dernière modification le : lundi 1 juillet 2019 - 09:46:47

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N. Boucheron, R. Tschismarov, L. Goschl, M. A. Moser, S. Lagger, et al.. CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2. Nature Immunology, Nature Publishing Group, 2014, 15, pp.439--48. ⟨10.1038/ni.2864⟩. ⟨hal-02168080⟩

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