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Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids
Open accessAbstract
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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“The proinflammatory adipokine chemerin was discovered to promote the chemotaxis of immature dendritic cells and macrophages via its receptor CMKLR1 (36).”
From Circulating Adipokine Levels in Nonobese Women with Polycystic Ovary Syndrome and in Nonobese Control Women: A Systematic Review and Meta-Analysis (2021) · cites this paper as [36]
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Metadata
- 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
- 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
- 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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