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

• Published in: Analytica chimica acta 2012-07, Vol.278 (1-2), p.95-102
• Main Authors: Poudel, Barun, Yoon, Dong-Sik, Lee, Jeong-Heon, Lee, Young-Mi, Kim, Dae-Ki
• Format: Article
• Language: English
• Subjects: Animals; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Cell Differentiation; Cell Proliferation - drug effects; Cells, Cultured; Collagen; 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; Human monocyte-derived dendritic cells; Humans; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukin-12; Interleukin-12 Subunit p40 - biosynthesis; Interleukin-12 Subunit p40 - immunology; Maturation; Melanoma; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Melanoma, Experimental - prevention & control; Mice; Mice, Inbred C57BL; Monocytes - cytology; Monocytes - immunology; 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; RNA, Small Interfering - genetics; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0008-8749; 0003-2670; 1090-2163
• DOI: 10.1016/j.cellimm.2012.07.004

► Role of collagen I and discoidin domain receptors (DDRs) on function of human monocyte-derived DCs was evaluated. ► Collagen I-human monocyte-derived dendritic cells (hDCs) upregulated release of cytokines and expression of costimulatory molecules. ► Depletion of DDR2 suppressed the functional ability of hDCs to proliferate T cells. ► Collagen I treated DCs reduced tumor burden in melanoma mice giving longer survival. ► Collagen I may enhance functional activities of DCs in immune response. 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.