Protease-activated receptor-2 signalling by tissue factor on dendritic cells suppresses antigen-specific CD4+ T-cell priming

Immunology. 2013 Jun;139(2):219-26. doi: 10.1111/imm.12073.


The precise function of tissue factor (TF) expressed by dendritic cells (DC) is uncertain. As well as initiating thrombin generation it can signal through protease-activated receptor 2 (PAR-2) when complexed with factor VIIa. We investigated the expression and function of TF on mouse bone marrow (BM) -derived DC; 20% of BM-derived DC expressed TF, which did not vary after incubation with lipopolysaccharide (LPS) or dexamethasone (DEX). However, the pro-coagulant activity of DEX-treated DC in recalcified plasma was 30-fold less than LPS-treated DC. In antigen-specific and allogeneic T-cell culture experiments, the TF on DEX-treated DC provided a signal through PAR-2, which contributed to the reduced ability of these cells to stimulate CD4(+) T-cell proliferation and cytokine production. In vivo, an inhibitory anti-TF antibody and a PAR-2 antagonist enhanced antigen-specific priming in two models where antigen was given without adjuvant, with an effect approximately 50% that seen with LPS, suggesting that a similar mechanism was operational physiologically. These data suggest a novel TF and PAR-2-dependent mechanism on DEX-DC in vitro and unprimed DC in vivo that contributes to the low immunogenicity of these cells. Targeting this pathway has the potential to influence antigen-specific CD4(+) T-cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Antigens / immunology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dexamethasone / pharmacology
  • Flow Cytometry
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptor, PAR-2 / antagonists & inhibitors
  • Receptor, PAR-2 / immunology*
  • Receptor, PAR-2 / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Thromboplastin / immunology*
  • Thromboplastin / metabolism
  • Thromboplastin / pharmacology


  • Antibodies
  • Antigens
  • Cytokines
  • Lipopolysaccharides
  • Receptor, PAR-2
  • Dexamethasone
  • Thromboplastin