CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2.
Nat Immunol
; 15(5): 439-448, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24681565
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-CBFß 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-CBFß complexes that otherwise induce a CD8(+) effector T cell-like program in CD4(+) T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Células Th1
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Linfócitos T CD8-Positivos
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Histona Desacetilase 1
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Histona Desacetilase 2
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Ano de publicação:
2014
Tipo de documento:
Article