PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon

Hiroshi Watarai, Etsuko Sekine, Sayo Inoue, Ryusuke Nakagawa, Tsuneyasu Kaisho, Masaru Taniguchi

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Type I interferons (IFNs) derived from plasmacytoid dendritic cells (PDCs) are critical for antiviral responses; however, the mechanisms underlying their production remain unclear. We have identified a receptor, PDC-TREM, which is associated with Plexin-A1 (PlxnA1) on the PDC cell surface and is preferentially expressed after TLR-stimulation. Limited TLR signals induced PDC-TREM expression but failed to induce IFN-α production. However, when coupled with Sema6D, a ligand for Plexin-A1, limited TLR-stimulation resulted in PDC-TREM-mediated DAP12-dependent phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular regulated kinase (Erk) 1/2 at 6-9 h, and IFN-α was produced. Inhibition of PDC-TREM expression by pdctrem-shRNA, blocking of PDC-TREM-binding with PlxnA1 by PDC-TREM mAb, and DAP12 deficiency all resulted in greatly reduced PDC-TREM-dependent activation of signaling molecules and IFN-α production. Thus, PDC-TREM is responsible for IFN-α production, whereas TLR signals are essential for PDC-TREM expression.

Original languageEnglish
Pages (from-to)2993-2998
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number8
DOIs
Publication statusPublished - 2008 Feb 26
Externally publishedYes

Fingerprint

Interferon Type I
Dendritic Cells
Interferons
1-Phosphatidylinositol 4-Kinase
Small Interfering RNA
Antiviral Agents
Phosphotransferases
Phosphorylation

Keywords

  • DAP12
  • Innate immunity
  • Plexin
  • Semaphorin
  • Toll-like receptor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon. / Watarai, Hiroshi; Sekine, Etsuko; Inoue, Sayo; Nakagawa, Ryusuke; Kaisho, Tsuneyasu; Taniguchi, Masaru.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 8, 26.02.2008, p. 2993-2998.

Research output: Contribution to journalArticle

Watarai, Hiroshi ; Sekine, Etsuko ; Inoue, Sayo ; Nakagawa, Ryusuke ; Kaisho, Tsuneyasu ; Taniguchi, Masaru. / PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 8. pp. 2993-2998.
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