Human plasmacytoid dendritic cell accumulation amplifies their type 1 interferon production

Clin Immunol. 2010 Jul;136(1):130-8. doi: 10.1016/j.clim.2010.02.014. Epub 2010 Mar 25.

Abstract

To determine the potential consequences of plasmacytoid dendritic cell (pDC) accumulation in tissue sites observed in several autoimmune diseases, we measured type 1 interferon production from circulating human pDCs as a function of pDC concentration. The effects of interferon-alpha and blockade of the type 1 interferon receptor (IFNAR) on human pDC type 1 interferon and interferon-inducible transcription and protein production were measured. Human pDCs became far more efficient producers of interferon-alpha at concentrations beyond those normally present in blood, through an IFNAR-dependent mechanism. Extracellular interferon-alpha increased pDC production of type 1 interferons. The accumulation of pDCs in diseased tissue sites allows marked non-linear amplification of type 1 interferon production locally. The role of the IFNAR-dependent mechanism of interferon production by human pDCs is greater than previously suggested. IFNAR blockade has potential for diminishing type 1 interferon production by all human cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Autocrine Communication / drug effects
  • Autocrine Communication / immunology
  • Carrier Proteins / genetics
  • Cell Count
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Endopeptidases / genetics
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Humans
  • Interferon Type I / genetics
  • Interferon Type I / metabolism*
  • Interferon alpha-2
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism
  • Interferon-alpha / pharmacology
  • Interferon-beta / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kinetics
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Myxovirus Resistance Proteins
  • Oligodeoxyribonucleotides / pharmacology
  • Oxidoreductases Acting on CH-CH Group Donors
  • Protein Isoforms / genetics
  • Proteins / genetics
  • RNA-Binding Proteins
  • Receptor, Interferon alpha-beta / antagonists & inhibitors
  • Receptor, Interferon alpha-beta / immunology
  • Recombinant Proteins
  • Toll-Like Receptor 9 / agonists
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics
  • Ubiquitin Thiolesterase
  • Ubiquitins / genetics
  • Ubiquitins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal
  • CPG-oligonucleotide
  • Carrier Proteins
  • Cytokines
  • HERC5 protein, human
  • IFIT1 protein, human
  • IFNAR2 protein, human
  • Interferon Type I
  • Interferon alpha-2
  • Interferon-alpha
  • Intracellular Signaling Peptides and Proteins
  • Myxovirus Resistance Proteins
  • Oligodeoxyribonucleotides
  • Protein Isoforms
  • Proteins
  • RNA-Binding Proteins
  • Recombinant Proteins
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Ubiquitins
  • interferon omega 1
  • Receptor, Interferon alpha-beta
  • ISG15 protein, human
  • Interferon-beta
  • Oxidoreductases Acting on CH-CH Group Donors
  • RSAD2 protein, human
  • Endopeptidases
  • USP18 protein, human
  • Ubiquitin Thiolesterase
  • GTP-Binding Proteins