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.
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5 November 2001
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October 29 2001
Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes
J.M. Weiss,
J.M. Weiss
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
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A.C. Renkl,
A.C. Renkl
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
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C.S. Maier,
C.S. Maier
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
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M. Kimmig,
M. Kimmig
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
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L. Liaw,
L. Liaw
4Center for Molecular Medicine, Maine Medical Center Research Institute, Portland, ME 04074
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T. Ahrens,
T. Ahrens
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
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S. Kon,
S. Kon
3Immuno-Biological Laboratory, Fujioka-shi, Gunma 375-0005, Japan
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M. Maeda,
M. Maeda
3Immuno-Biological Laboratory, Fujioka-shi, Gunma 375-0005, Japan
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H. Hotta,
H. Hotta
2Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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T. Uede,
T. Uede
2Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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J.C. Simon
J.C. Simon
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
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J.M. Weiss
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
A.C. Renkl
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
C.S. Maier
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
M. Kimmig
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
L. Liaw
4Center for Molecular Medicine, Maine Medical Center Research Institute, Portland, ME 04074
T. Ahrens
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
S. Kon
3Immuno-Biological Laboratory, Fujioka-shi, Gunma 375-0005, Japan
M. Maeda
3Immuno-Biological Laboratory, Fujioka-shi, Gunma 375-0005, Japan
H. Hotta
2Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
T. Uede
2Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
J.C. Simon
1Department of Dermatology, University of Freiburg, D-79104 Freiburg, Germany
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: [email protected]
J.M. Weiss and A.C. Renkl contributed equally to this work.
*
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.
Received:
October 20 2000
Revision Received:
July 26 2001
Accepted:
September 06 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2001
J Exp Med (2001) 194 (9): 1219–1230.
Article history
Received:
October 20 2000
Revision Received:
July 26 2001
Accepted:
September 06 2001
Citation
J.M. Weiss, A.C. Renkl, C.S. Maier, M. Kimmig, L. Liaw, T. Ahrens, S. Kon, M. Maeda, H. Hotta, T. Uede, J.C. Simon; Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes . J Exp Med 5 November 2001; 194 (9): 1219–1230. doi: https://doi.org/10.1084/jem.194.9.1219
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