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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 αv 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. dendritic cells Langerhans cells integrins CD44 osteopontin Footnotes ↵ * Abbreviations used in this paper: ANOVA, analysis of variance; CHS, contact hypersensitivity; DC, dendritic cell; ECM, extracellular matrix; LC, Langerhans cell; OPN, osteopontin; TNCB, Trinitro-chloro-benzene. J.M. Weiss and A.C. Renkl contributed equally to this work. Submitted: 20 October 2000 Accepted: 6 September 2001 Revision received 26 July 2001
The Journal of Experimental Medicine – Rockefeller University Press
Published: Nov 5, 2001
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