Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids

By Valérie Wittamer, J. Franssen, M. Vulcano, J. Mirjolet, E. Le Poul, I. Migeotte, S. Brézillon, R. Tyldesley, C. Blanpain, M. Detheux and 5 more. Journal of Experimental Medicine, 2003

916 citations recorded by the source corpus.

Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein–coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42–p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.

Subfields: Epidemiology, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/afdca6b63eb62fede3bb2137bd3e293465b431d7

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In Epidemiology

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Citations in the corpus

• Adipokines Mediate Inflammation and Insulin Resistance (2013, background): “Chemerin is a ligand of the G protein-coupled receptor ChemR23 (Wittamer et al., 2003) and expressed in most tissues except leukocytes.”
• The genetic design of signaling cascades to record receptor activation (2008, methodology): “The relatively weak response of GPR1 to chemerin using a calcium mobilization assay may explain a previous study that did not detect chemerin-mediated activation of GPR1 (23).”
• Resolvin E1 Selectively Interacts with Leukotriene B4 Receptor BLT1 and ChemR23 to Regulate Inflammation1 (2007, background): “ChemR23 is abundantly expressed in macrophages and dendritic cells (DC), but apparently not as much in PMN (13).”
• Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1 (2005, methodology): “These results are in line with the reported properties of this peptide ligand (17).”
• Chemerin is a novel adipokine associated with obesity and metabolic syndrome. (2007, background): “Chemerin has been expressed in a number of tissues, including liver, pancreas, and lung (16–18), whereas expression of CMKLR1 has previously been found predominantly in cells of the immune system, such as neutrophils, activated macrophages, and dendritic cells (17).”