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Original Article

¹ Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
² Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
³ Immuno-Biological Laboratory, Fujioka-shi, Gunma 375-0005, Japan
⁴ Center for Molecular Medicine, Maine Medical Center Research Institute, Portland, ME 04074

Address correspondence to Johannes M. Weiss, Department of Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany. Phone: 49-761-270-6701; Fax: 49-761-270-6829; E-mail: weiss{at}haut.ukl.uni-freiburg.de

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 v 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.

Key Words: dendritic cells • Langerhans cells • integrins • CD44 • osteopontin

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