Abstract
Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / immunology
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Cell Differentiation
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Cell Movement / immunology*
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Cells, Cultured
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Chemotaxis
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Dendritic Cells / cytology
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Dendritic Cells / immunology
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Dermatitis, Allergic Contact / immunology*
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Disease Models, Animal
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Epidermis / immunology
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Hyaluronan Receptors / immunology
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Injections, Intradermal
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Langerhans Cells / cytology
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Langerhans Cells / immunology*
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Lymph Nodes / cytology
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Lymph Nodes / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Osteopontin
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Receptors, Vitronectin / biosynthesis
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Receptors, Vitronectin / immunology
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Sialoglycoproteins / administration & dosage
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Sialoglycoproteins / genetics
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Sialoglycoproteins / immunology*
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Up-Regulation
Substances
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Antibodies, Monoclonal
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Hyaluronan Receptors
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Receptors, Vitronectin
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Sialoglycoproteins
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Spp1 protein, mouse
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Osteopontin