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CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2.
- Source :
-
Nature immunology [Nat Immunol] 2014 May; Vol. 15 (5), pp. 439-448. Date of Electronic Publication: 2014 Mar 30. - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Cell Differentiation genetics
Cell Lineage genetics
Cells, Cultured
Core Binding Factor alpha Subunits metabolism
Core Binding Factor beta Subunit metabolism
Cytokines metabolism
Cytotoxicity, Immunologic genetics
Histocompatibility Antigens Class II genetics
Histocompatibility Antigens Class II metabolism
Histone Deacetylase 1 genetics
Histone Deacetylase 2 genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Binding
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Histone Deacetylase 1 metabolism
Histone Deacetylase 2 metabolism
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 15
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 24681565
- Full Text :
- https://doi.org/10.1038/ni.2864