Collagen I enhances functional activities of human monocyte-derived dendritic cells via discoidin domain receptor 2

Cell Immunol. 2012 Jul-Aug;278(1-2):95-102. doi: 10.1016/j.cellimm.2012.07.004. Epub 2012 Aug 3.

Abstract

We evaluated the involvement of collagen and their discoidin domain receptors (DDRs), DDR1 and DDR2, on the activation of human monocyte-derived dendritic cells (hDCs). DDR2 was markedly expressed on mature hDCs in comparison to immature ones. Collagen I enhanced the release of IL-12p40, TNF-α and IFN-γ by hDCs. Additionally, hDCs exhibited enhanced expression of costimulatory molecules, and potent functional activities which, in turn, has therapeutic value. Interestingly, DDR2 depletion showed decrease in capacity of hDCs to stimulate T cells proliferation, whereas DDR1 silencing had no significant affect. These data demonstrate that DDR2 enhances hDCs activation and contributes to their functional activities. In addition, application of collagen I treated dendritic cells (DCs) vaccine reduced tumor burden giving longer survival in melanoma mice. Our study suggests that collagen I may enhance functional activities of DCs in immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use
  • Cell Differentiation
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collagen Type I / immunology*
  • Collagen Type I / pharmacology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Discoidin Domain Receptor 1
  • Discoidin Domain Receptors
  • Female
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-12 Subunit p40 / biosynthesis
  • Interleukin-12 Subunit p40 / immunology
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / cytology
  • Monocytes / immunology
  • RNA, Small Interfering / genetics
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / immunology*
  • Receptors, Mitogen / antagonists & inhibitors
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Cancer Vaccines
  • Collagen Type I
  • Interleukin-12 Subunit p40
  • RNA, Small Interfering
  • Receptors, Mitogen
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • DDR1 protein, human
  • Discoidin Domain Receptor 1
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases