Critical role of IkappaB Kinase alpha in TLR7/9-induced type I IFN production by conventional dendritic cells.
Copyright policy )Critical role of IkappaB Kinase alpha in TLR7/9-induced type I IFN production by conventional dendritic cells.
A plasmacytoid dendritic cell (DC) can produce large amounts of type I IFNs after sensing nucleic acids through TLR7 and TLR9. IkappaB kinase alpha (IKKalpha) is critically involved in this type I IFN production through its interaction with IFN regulatory factor-7. In response to TLR7/9 signaling, conventional DCs can also produce IFN-beta but not IFN-alpha in a type I IFN-independent manner. In this study, we showed that IKKalpha was required for production of IFN-beta, but not of proinflammatory cytokines, by TLR7/9-stimulated conventional DCs. Importantly, IKKalpha was dispensable for IFN-beta gene upregulation by TLR4 signaling. Biochemical analyses indicated that IKKalpha exerted its effects through its interaction with IFN regulatory factor-1. Furthermore, IKKalpha was involved in TLR9-induced type I IFN-independent IFN-beta production in vivo. Our results show that IKKalpha is a unique molecule involved in TLR7/9-MyD88-dependent type I IFN production through DC subset-specific mechanisms.
- Yokohama City University Japan
Mice, Knockout, Membrane Glycoproteins, Gene Expression, Electrophoretic Mobility Shift Assay, Enzyme-Linked Immunosorbent Assay, Dendritic Cells, Interferon-beta, Blotting, Northern, I-kappa B Kinase, Mice, Gene Expression Regulation, Toll-Like Receptor 7, Toll-Like Receptor 9, Animals, Immunoprecipitation, Signal Transduction
Mice, Knockout, Membrane Glycoproteins, Gene Expression, Electrophoretic Mobility Shift Assay, Enzyme-Linked Immunosorbent Assay, Dendritic Cells, Interferon-beta, Blotting, Northern, I-kappa B Kinase, Mice, Gene Expression Regulation, Toll-Like Receptor 7, Toll-Like Receptor 9, Animals, Immunoprecipitation, Signal Transduction
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