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Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction.
- Source :
- Journal of Experimental Medicine; 3/21/2005, Vol. 201 Issue 6, p915-923, 9p, 2 Diagrams, 3 Graphs
- Publication Year :
- 2005
-
Abstract
- Toll-like receptors (TLRs) recognize microbial pathogens and trigger innate immune responses. Among TLR family members, TLR7, TLR8, and TLR9 induce interferon (IFN)-α in plasmacytoid dendritic cells (pDCs). This induction requires the formation of a complex consisting of the adaptor MyD88, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and IFN regulatory factor (IRF) 7. Here we show an essential role of IL-1 receptor-associated kinase (IRAK)-1 in TLR7- and TLR9-mediated IRF7 signaling pathway. IRAK-1 directly bound and phosphorylated IRF7 in vitro. The kinase activity of IRAK-1 was necessary for transcriptional activation of IRF7. TLR7- and TLR9-mediated IFN-α production was abolished in Irak-1-deficient mice, whereas inflammatory cytokine production was not impaired. Despite normal activation of NF-κB and mitogen-activated protein kinases, IRF7 was not activated by a TLR9 ligand in Irak-1-deficient pDCs. These results indicated that IRAK-1 is a specific regulator for TLR7- and TLR9-mediated IFN-α induction in pDCs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00221007
- Volume :
- 201
- Issue :
- 6
- Database :
- Supplemental Index
- Journal :
- Journal of Experimental Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 26917588
- Full Text :
- https://doi.org/10.1084/jem.20042372