T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt.
Nat Immunol
; 12(1): 96-104, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-21151104
ABSTRACT
Overactive responses by interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are tightly linked to the development of autoimmunity, yet the factors that negatively regulate the differentiation of this lineage remain unknown. Here we report that the transcription factor T-bet suppressed development of the T(H)17 cell lineage by inhibiting transcription of Rorc (which encodes the transcription factor RORγt). T-bet interacted with the transcription factor Runx1, and this interaction blocked Runx1-mediated transactivation of Rorc. T-bet Tyr304 was required for formation of the T-bet-Runx1 complex, for blockade of Runx1 activity and for inhibition of the T(H)17 differentiation program. Our data reinforce the idea of master regulators that shape immune responses by simultaneously activating one genetic program while silencing the activity of competing regulators in a common progenitor cell.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas com Domínio T
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Encefalomielite Autoimune Experimental
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Subunidade alfa 2 de Fator de Ligação ao Core
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Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares
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Células Th17
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos