Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model.
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.
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
Souphalone
S
Luangsay
Valérie
V
Wittamer
Benjamin
B
Bondue
Olivier
O
De Henau
Laurie
L
Rouger
Maryse
M
Brait
Jean-Denis
JD
Franssen
Patricia
P
de Nadai
François
F
Huaux
Marc
M
Parmentier
D000208:Acute Disease; D000331:Aequorin / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001059:Apoproteins / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D018925:Chemokines; D002630:Chemotactic Factors / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism
D001059:Apoproteins; C486456:CMKLR1 protein, mouse; D018925:Chemokines; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D010455:Peptides; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; C060014:apoaequorin; C523686:chemerin protein, mouse; D000331:Aequorin; D002118:Calcium