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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cancer Vaccines / immunology
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Cancer Vaccines / therapeutic use
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Cell Differentiation
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Cell Proliferation / drug effects
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Cells, Cultured
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Collagen Type I / immunology*
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Collagen Type I / pharmacology
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Dendritic Cells / transplantation
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Discoidin Domain Receptor 1
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Discoidin Domain Receptors
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Female
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Gene Expression / drug effects
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Gene Expression / immunology
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Humans
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology
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Interleukin-12 Subunit p40 / biosynthesis
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Interleukin-12 Subunit p40 / immunology
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Melanoma, Experimental / immunology
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Melanoma, Experimental / pathology
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Melanoma, Experimental / prevention & control
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Mice
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Mice, Inbred C57BL
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Monocytes / cytology
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Monocytes / immunology
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RNA, Small Interfering / genetics
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / immunology*
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Receptors, Mitogen / antagonists & inhibitors
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Receptors, Mitogen / genetics
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Receptors, Mitogen / immunology*
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / immunology
Substances
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Cancer Vaccines
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Collagen Type I
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Interleukin-12 Subunit p40
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RNA, Small Interfering
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Receptors, Mitogen
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Tumor Necrosis Factor-alpha
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Interferon-gamma
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DDR1 protein, human
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Discoidin Domain Receptor 1
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Discoidin Domain Receptors
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Receptor Protein-Tyrosine Kinases