Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization.
Nat Immunol
; 13(7): 642-50, 2012 May 20.
Article
em En
| MEDLINE
| ID: mdl-22610140
ABSTRACT
Emerging concepts suggest that the functional phenotype of macrophages is regulated by transcription factors that define alternative activation states. We found that RBP-J, the main nuclear transducer of signaling via Notch receptors, augmented Toll-like receptor 4 (TLR4)-induced expression of key mediators of classically activated M1 macrophages and thus of innate immune responses to Listeria monocytogenes. Notch-RBP-J signaling controlled expression of the transcription factor IRF8 that induced downstream M1 macrophage-associated genes. RBP-J promoted the synthesis of IRF8 protein by selectively augmenting kinase IRAK2-dependent signaling via TLR4 to the kinase MNK1 and downstream translation-initiation control through eIF4E. Our results define a signaling network in which signaling via Notch-RBP-J and TLRs is integrated at the level of synthesis of IRF8 protein and identify a mechanism by which heterologous signaling pathways can regulate the TLR-induced inflammatory polarization of macrophages.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fatores Reguladores de Interferon
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Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina
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Receptores Notch
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Inflamação
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Macrófagos
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos