Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization.
Citation:
Xu H*, Zhu J*, Smith S*, Foldi J, Zhao B, Chung AY, Outtz H, Kitajewski J, Shi C, Weber S, Saftig P, Li Y, Ozato K, Blobel CP, Ivashkiv LB, Hu X., Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization., Nature Immunology, 13, 7, 2012, 642 - 650Download Item:
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
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http://people.tcd.ie/smithsiDescription:
PUBLISHED*Joint First Authors
Author: SMITH, SINEAD
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Journal ArticleCollections
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Nature Immunology13
7
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Full text availableKeywords:
macrophagesSubject (TCD):
Immunology, Inflammation & InfectionMetadata
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