Cutting edge: Critical role of IκB kinaseain TLR7/9-induced type I IFN production by conventional dendritic cells

Katsuaki Hoshino, Izumi Sasaki, Takahiro Sugiyama, Takahiro Yano, Chihiro Yamazaki, Teruhito Yasui, Hitoshi Kikutani, Tsuneyasu Kaisho

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

A plasmacytoid dendritic cell (DC) can produce large amounts of type I IFNs after sensing nucleic acids through TLR7 and TLR9. IκB kinase α (IKKα) 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-β but not IFN-α in a type I IFN-independent manner. In this study, we showed that IKKα was required for production of IFN-β, but not of proinflammatory cytokines, by TLR7/9-stimulated conventional DCs. Importantly, IKKα was dispensable for IFN-β gene upregulation by TLR4 signaling. Biochemical analyses indicated that IKKα exerted its effects through its interaction with IFN regulatory factor-1. Furthermore, IKKα was involved in TLR9-induced type I IFN-independent IFN-β production in vivo. Our results show that IKKα is a uniquemolecule involved in TLR7/9-MyD88-dependent type I IFN production through DC subset-specific mechanisms.

Original languageEnglish
Pages (from-to)3341-3345
Number of pages5
JournalJournal of Immunology
Volume184
Issue number7
DOIs
Publication statusPublished - Apr 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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