Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature.
Immunity
; 27(5): 786-800, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-18024188
ABSTRACT
The CD4(+)CD25(+) lineage of regulatory T (Treg) cells plays a key role in controlling immune and autoimmune responses and is characterized by a unique transcriptional signature. The transcription factor Foxp3 had been thought to determine the Treg cell lineage, a hypothesis challenged by recent observations. We have performed a cross-sectional analysis of the Treg cell signature in Treg-like cells generated under a number of conditions, with or without Foxp3, to delineate the elements that can be ascribed to T cell activation, interleukin-2, transforming growth factor-beta (TGF-beta) signaling, or Foxp3 itself. These influences synergized to determine many of the signature's components. Much of the Treg cell signature was not ascribable to Foxp3 because it contained gene clusters that are coregulated with, but not transactivated by, Foxp3. Thus, a higher level of regulation upstream of Foxp3 determines the lineage, distinct from elements downstream of Foxp3 that are essential for its regulatory properties.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Diferenciação Celular
/
Regulação da Expressão Gênica
/
Linfócitos T Reguladores
/
Fatores de Transcrição Forkhead
Limite:
Animals
Idioma:
En
Revista:
Immunity
Ano de publicação:
2007
Tipo de documento:
Article