Cutting Edge: Critical Role of IκB Kinase α 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. I kappa B kinase alpha (IKK alpha) 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 IKK alpha was required for production of IFN-beta, but not of proinflammatory cytokines, by TLR7/9-stimulated conventional DCs. Importantly, IKK alpha was dispensable for IFN-beta gene upregulation by TLR4 signaling. Biochemical analyses indicated that IKK alpha exerted its effects through its interaction with IFN regulatory factor-1. Furthermore, IKK alpha was involved in TLR9-induced type I IFN-independent IFN-beta production in vivo. Our results show that IKK alpha is a unique molecule involved in TLR7/9-MyD88-dependent type I IFN production through DC subset-specific mechanisms. The journal of Immunology, 2010, 184: 3341-3345.