Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes

Weiss , J.M.; Renkl , A.C.; Maier , C.S.; Kimmig , M.; Liaw , L.; Ahrens , T.; Kon , S.; Maeda , M.; Hotta , H.; Uede , T.; Simon , J.C.

doi:10.1084/jem.194.9.1219

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Article| 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,

A.C. Renkl,

C.S. Maier,

M. Kimmig,

L. Liaw,

T. Ahrens,

S. Kon,

M. Maeda,

H. Hotta,

T. Uede,

J.C. Simon

Author and Article Information

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.

https://doi.org/10.1084/jem.194.9.1219

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.

The Rockefeller University Press

2001

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