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*Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium;
Euroscreen, Gosselies, Belgium; and
Laboratoire de Toxicologie Industrielle, Université Catholique de Louvain, Brussels, Belgium
Chemerin is the ligand of the ChemR23 receptor and a chemoattractant factor for human immature dendritic cells (DCs), macrophages, and NK cells. In this study, we characterized the mouse chemerin/ChemR23 system in terms of pharmacology, structure-function, distribution, and in vivo biological properties. Mouse chemerin is synthesized as an inactive precursor (prochemerin) requiring, as in human, the precise processing of its C terminus for generating an agonist of ChemR23. Mouse ChemR23 is highly expressed in immature plasmacytoid DCs and at lower levels in myeloid DCs, macrophages, and NK cells. Mouse prochemerin is expressed in most epithelial cells acting as barriers for pathogens but not in leukocytes. Chemerin promotes calcium mobilization and chemotaxis on DCs and macrophages and these functional responses were abrogated in ChemR23 knockout mice. In a mouse model of acute lung inflammation induced by LPS, chemerin displayed potent anti-inflammatory properties, reducing neutrophil infiltration and inflammatory cytokine release in a ChemR23-dependent manner. ChemR23 knockout mice were unresponsive to chemerin and displayed an increased neutrophil infiltrate following LPS challenge. Altogether, the mouse chemerin/ChemR23 system is structurally and functionally conserved between human and mouse, and mouse can therefore be considered as a good model for studying the anti-inflammatory role of this system in the regulation of immune responses and inflammatory diseases.
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1 This work was supported by the Interuniversity Attraction Poles Programme, Belgian State, Belgian Science Policy; the Actions de Recherche Concertées of the Communauté Française de Belgique; the European Union (LSHB-CT-2005–518167/ INNOCHEM); the Fonds de la Recherche Scientifique Médicale of Belgium; the Walloon Region (Programme d’excellence "CIBLES"); The Fonds Ithier; the Fédération Belge contre le Cancer; and the Fondation Médicale Reine Elisabeth to M.P. B.B. and O.D.H. are aspirants of the Belgian National Fund for Scientific Research.
2 These authors contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Marc Parmentier, I.R.I.B.H.M. Université Libre de Bruxelles, Campus Erasme, Route de Lennik 808, B-1070, Brussels, Belgium. E-mail address: mparment{at}ulb.ac.be
4 Abbreviations used in this paper: DC, dendritic cell; AM, alveolar macrophage; BAL, bronchoalveolar lavage; BALF, bronchoalveolar lavage fluid; BMDC, bone marrow-derived DC; KO, knockout; mDC, myeloid DC; pDC, plasmacytoid DC; WT, wild type.
5 The online version of this article contains supplemental material.
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