dc.contributor.author | SMITH, SINEAD | en |
dc.date.accessioned | 2014-12-15T13:31:52Z | |
dc.date.available | 2014-12-15T13:31:52Z | |
dc.date.issued | 2012 | en |
dc.date.submitted | 2012 | en |
dc.identifier.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 - 650 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/72474 | |
dc.description | PUBLISHED | en |
dc.description | *Joint First Authors | en |
dc.description.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 | en |
dc.format.extent | 642 | en |
dc.format.extent | 650 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Nature Immunology | en |
dc.relation.ispartofseries | 13 | en |
dc.relation.ispartofseries | 7 | en |
dc.rights | Y | en |
dc.subject | macrophages | en |
dc.title | Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/smithsi | en |
dc.identifier.rssinternalid | 82538 | en |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.identifier.rssuri | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513378/ | en |
dc.identifier.orcid_id | 0000-0003-3460-3590 | en |