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

Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2993-8. doi: 10.1073/pnas.0710351105. Epub 2008 Feb 19.

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-alpha 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-alpha 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-alpha production. Thus, PDC-TREM is responsible for IFN-alpha production, whereas TLR signals are essential for PDC-TREM expression.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Base Sequence
  • Blotting, Western
  • Cells, Cultured
  • Computational Biology
  • Cytokines / analysis
  • DNA Primers / genetics
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Regulation / immunology*
  • Interferon Type I / biosynthesis*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • RNA Interference
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / immunology*
  • Receptors, Cell Surface / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Semaphorins / metabolism
  • Sequence Analysis, DNA
  • Spleen / metabolism
  • Toll-Like Receptors / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal
  • Cytokines
  • DNA Primers
  • Interferon Type I
  • Nerve Tissue Proteins
  • PDC-TREM protein, mouse
  • Plxna1 protein, mouse
  • Receptors, Cell Surface
  • Sema6d protein, mouse
  • Semaphorins
  • Toll-Like Receptors
  • Tyrobp protein, mouse

Associated data

  • GENBANK/AB372005