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Notch-RBP-J Signaling Regulates IRF8 to Promote Inflammatory Macrophage Polarization
- Source :
- Nature immunology
- Publication Year :
- 2012
-
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.
- Subjects :
- Inflammation
Male
endocrine system
Receptors, Notch
Macrophages
Cell Polarity
Macrophage Activation
Protein Serine-Threonine Kinases
Article
DNA-Binding Proteins
Mice, Inbred C57BL
Toll-Like Receptor 4
Mice
Interleukin-1 Receptor-Associated Kinases
Gene Expression Regulation
Immunoglobulin J Recombination Signal Sequence-Binding Protein
Interferon Regulatory Factors
Animals
Female
Listeriosis
Signal Transduction
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 15292916 and 15292908
- Volume :
- 13
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Nature immunology
- Accession number :
- edsair.pmid..........1d01940fb97c475f49805ebe063fddcd