Reference - Detail
| RRC ID | 5322 |
|---|---|
| Author | Molle C, Nguyen M, Flamand V, Renneson J, Trottein F, De Wit D, Willems F, Goldman M, Goriely S. |
| Title | IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3. |
| Journal | J Immunol |
| Abstract |
IL-27 is a heterodimeric cytokine composed of EBV-induced gene 3 and p28. Produced by dendritic cells (DCs) in response to TLR ligands, IL-27 recently emerged as a key regulator of inflammatory responses. In this study, we first demonstrate that Toll/IL-1R-containing adaptor inducing IFN-beta and its associated IFN regulatory factor (IRF) 3 transcription factor are critically involved in IL-27p28 expression in mouse DCs stimulated by TLR ligands. We then show that IL-27 serum levels are dramatically reduced in IRF3(-/-) upon LPS injection, indicating a critical role for IRF3 in TLR4-mediated IL-27 production in vivo. We identified an IRF3-binding site within the IL-27p28 promoter region which is required for IL-27p28 gene activation in reporter gene assays. In human DCs, IL-27p28 mRNA was preferentially induced by Toll/IL-1R-containing adaptor inducing IFN-beta-coupled TLR ligands and following CMV infection. Furthermore, chromatin immunoprecipitation studies demonstrate that IRF3 is recruited to the endogenous p28 promoter in TLR4-stimulated human DCs. We conclude that IRF3 activation is a master switch for IL-27 synthesis. |
| Volume | 178(12) |
| Pages | 7607-15 |
| Published | 2007-6-15 |
| DOI | 10.4049/jimmunol.178.12.7607 |
| PII | 178/12/7607 |
| PMID | 17548596 |
| MeSH | Adaptor Proteins, Vesicular Transport / metabolism* Amino Acid Sequence Animals Binding Sites Chromatin Immunoprecipitation Dendritic Cells / immunology Gene Expression Regulation* Humans Interferon Regulatory Factor-3 / genetics Interferon Regulatory Factor-3 / metabolism* Interferon-beta / metabolism Interleukins / biosynthesis Interleukins / blood Interleukins / genetics* Lipopolysaccharides / immunology Mice Minor Histocompatibility Antigens Molecular Sequence Data Myeloid Differentiation Factor 88 / metabolism Promoter Regions, Genetic Receptors, Cytokine / genetics Receptors, Interleukin-1 / metabolism Toll-Like Receptor 4 / agonists Toll-Like Receptors / metabolism Transcriptional Activation |
| IF | 4.886 |
| Times Cited | 97 |
| WOS Category | IMMUNOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC00858 |