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The Journal of Immunology, 2007, 178: 5305-5311.
Copyright © 2007 by The American Association of Immunologists, Inc.

Chemokine Receptor CCR2 but Not CCR5 or CCR6 Mediates the Increase in Pulmonary Dendritic Cells during Allergic Airway Inflammation1

Lander J. Robays2,*, Tania Maes*, Serge Lebecque{dagger}, Sergio A. Lira{ddagger}, William A. Kuziel§, Guy G. Brusselle*, Guy F. Joos* and Karim V. Vermaelen2,*

* Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium; {dagger} Institut National de la Santé et de la Recherche Médicale Unité 503, Centre d’Etudes et de Recherches en Virologie et Immunologie, Lyon, France; {ddagger} Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029; and § PDL BioPharma, Fremont, CA 94555

Increased numbers of pulmonary dendritic cells (DCs) are recruited to the lungs during allergic airway inflammation and contribute to the maintenance of the inflammatory immune response. The chemokine receptors that directly control DC accumulation into the lungs are largely unknown. To explore this issue, we generated mixed bone marrow chimeric mice containing both wild-type and knockout cells for a given chemokine receptor. After induction of allergic airway inflammation, we specifically tracked and compared chemokine receptor knockout vs wild-type DC populations through various lung compartments. Using this approach, we show that CCR2, but not CCR5 or CCR6, directly controls the accumulation of DCs into allergic lungs. Furthermore, the size of inflammatory monocyte populations in peripheral blood was strikingly CCR2 dependent, suggesting that CCR2 primarily mediates the release of monocytic DC precursors into the bloodstream.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Concerted Research Initiative Ghent University Grants BOF/GOA 12050698 and BOF/GOA 12.515.04.

2 Address correspondence and reprint requests to Dr. Karim V. Vermaelen, Department of Respiratory Diseases 7K12 IE, University Hospital Ghent, De Pintelaan 185, Ghent, Belgium; E-mail address: karim.vermaelen{at}ugent.be or Dr. Lander J. Robays, Department of Respiratory Diseases 7K12 IE, University Hospital Ghent, De Pintelaan 185, Ghent, Belgium; E-mail addresses: lander.robays{at}ugent.be

3 Abbreviations used in this paper: DC, dendritic cell; BAL, bronchoalveolar lavage; FSC, forward scatter; KO, knockout; LN, lymph node; PBM, peripheral blood monocyte; SSC, side scatter; WT, wild type.




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