Cited by 891Chemokine receptors and signalingImmune Response and InflammationAntimicrobial Peptides and Activities

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

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Wittamer, Valérie, Franssen, Jean-Denis, Vulcano, Marisa, Mirjolet, Jean-François, Le Poul, Emmanuel, Migeotte, Isabelle, Brézillon, Stéphane, Tyldesley, Richard, Blanpain, Cédric, Detheux, Michel, Mantovani, Alberto, Sozzani, Silvano, Vassart, Gilbert, Parmentier, Marc, Communi, David·2003·The Journal of Experimental Medicine

DOI 10.1084/jem.20030382PMC PMC2194212

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Abstract

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.

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Authors: Wittamer, V., Franssen, J.-D., Vulcano, M., Mirjolet, J.-F., Le Poul, E., Migeotte, I., Brézillon, S., Tyldesley, R., Blanpain, C., Detheux, M., Mantovani, A., Sozzani, S., Vassart, G., Parmentier, M., & Communi, D.
Affiliations: 1Institut de Recherche en Biologie Humaine et Moléculaire, B-1070 Brussels, Belgium
Euroscreen (Belgium) (BE)
Mario Negri Institute for Pharmacological Research (IT)
2Euroscreen s.a., B-6041 Gosselies, Belgium
4Micromass Ltd., Manchester M23 9LZ, United Kingdom
University of Milan (IT)
Corresponding author: Parmentier, Marc
ORCID: Vulcano, Marisa
Migeotte, Isabelle
Mantovani, Alberto
Sozzani, Silvano
Vassart, Gilbert
Parmentier, Marc
Communi, David
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2003-10-06
Volume: 198
Issue: 7
Pages: 977-985
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20030382
PMC: PMC2194212
OpenAlex: W2168015220
Cited by: 888
References: 31
Citations by year: 2026: 22 · 2025: 33 · 2024: 38 · 2023: 40 · 2022: 50 · 2021: 42 · 2020: 65 · 2019: 43 · 2018: 57 · 2017: 44 · 2016: 55 · 2015: 55 · 2014: 63 · 2013: 53 · 2012: 51
FWCI: 4.79
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders: Waalse Gewest
Fédération Wallonie-Bruxelles
Associazione Italiana per la Ricerca sul Cancro
Fondation Médicale Reine Elisabeth
Topics: Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
Keywords: chemerin, ChemR23, G protein-coupled receptors, dendritic cells, macrophages, antigen-presenting cells, chemoattractants, proteolytic processing, intracellular calcium release, cAMP inhibition, MAPK phosphorylation, chemotaxis, kininogen, cystatin
MeSH terms: Amino Acid Sequence, Antigen-Presenting Cells, Calcium, Cell Movement, Dendritic Cells, Humans, Molecular Sequence Data, Chemokines, Receptors, Chemokine, Intercellular Signaling Peptides and Proteins

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

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