| RRC ID |
5322
|
| 著者 |
Molle C, Nguyen M, Flamand V, Renneson J, Trottein F, De Wit D, Willems F, Goldman M, Goriely S.
|
| タイトル |
IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3.
|
| ジャーナル |
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.
|
| 巻・号 |
178(12)
|
| ページ |
7607-15
|
| 公開日 |
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
|
| 引用数 |
97
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00858 |
