TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells.
Nat Immunol
; 15(7): 646-656, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24836425
ABSTRACT
The transcription factors TCF-1 and LEF-1 are essential for early T cell development, but their roles beyond the CD4(+)CD8(+) double-positive (DP) stage are unknown. By specific ablation of these factors in DP thymocytes, we demonstrated that deficiency in TCF-1 and LEF-1 diminished the output of CD4(+) T cells and redirected CD4(+) T cells to a CD8(+) T cell fate. The role of TCF-1 and LEF-1 in the CD4-versus-CD8 lineage 'choice' was mediated in part by direct positive regulation of the transcription factor Th-POK. Furthermore, loss of TCF-1 and LEF-1 unexpectedly caused derepression of CD4 expression in T cells committed to the CD8(+) lineage without affecting the expression of Runx transcription factors. Instead, TCF-1 physically interacted with Runx3 to cooperatively silence Cd4. Thus, TCF-1 and LEF-1 adopted distinct genetic 'wiring' to promote the CD4(+) T cell fate and establish CD8(+) T cell identity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Linfócitos T CD4-Positivos
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Antígenos CD4
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Linfócitos T CD8-Positivos
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Fator 1 de Ligação ao Facilitador Linfoide
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Fator 1 de Transcrição de Linfócitos T
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Subunidade alfa 3 de Fator de Ligação ao Core
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article