Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction
| Autor: | Ken Ishii, Hiroki Kato, Cevayir Coban, Masahiro Yamamoto, Shintaro Sato, Osamu Takeuchi, Shizuo Akira, Fumihiko Takeshita, Tomonori Hirotani, Satoshi Uematsu, Taro Kawai, Michiyuki Matsuda |
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| Rok vydání: | 2005 |
| Předmět: |
Interferon Regulatory Factor-7
Plasma Cells Immunology Receptors Cell Surface Biology Receptors Tumor Necrosis Factor Article Cell Line Mice Interferon Interleukin-1 Receptor-Associated Kinases medicine Animals Humans Immunology and Allergy Receptors Immunologic Kinase activity Adaptor Proteins Signal Transducing Mice Knockout TNF Receptor-Associated Factor 6 Toll-like receptor Membrane Glycoproteins NF-kappa B Interferon-alpha TLR9 hemic and immune systems Dendritic Cells Antigens Differentiation Cell biology DNA-Binding Proteins Gene Expression Regulation Toll-Like Receptor 7 Toll-Like Receptor 9 Myeloid Differentiation Factor 88 Cancer research IRF7 Mitogen-Activated Protein Kinases Signal transduction Protein Kinases Signal Transduction medicine.drug |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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