| First Author | Molle C | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 12 | Pages | 7607-15 |
| PubMed ID | 17548596 | Mgi Jnum | J:148591 |
| Mgi Id | MGI:3845739 | Doi | 10.4049/jimmunol.178.12.7607 |
| Citation | Molle C, et al. (2007) IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3. J Immunol 178(12):7607-15 |
| abstractText | 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. |
