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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3625-3632.
Prepublished online as a Blood First Edition Paper on January 3, 2007; DOI 10.1182/blood-2006-08-038844.
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CHEMOKINES, CYTOKINES, AND INTERLEUKINS
The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues
Silvia Parolini1,
Amerigo Santoro2,
Emanuela Marcenaro3,
Walter Luini4,
Luisa Massardi5,
Fabio Facchetti2,
David Communi6,
Marc Parmentier6,
Alessandra Majorana7,
Marina Sironi8,
Giovanna Tabellini1,
Alessandro Moretta3, and
Silvano Sozzani5
1 Section of Histology, University of Brescia, Brescia, Italy;
2 Section of Pathology, University of Brescia, Brescia, Italy;
3 Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, University of Genoa, Genoa, Italy;
4 Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy;
5 Section of General Pathology and Immunology, University of Brescia, Brescia, Italy;
6 Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels, Belgium;
7 Department of Dental Medicine, University of Brescia, Spedali Civili Brescia, Brescia, Italy;
8 Istituto Clinico Humanitas, Rozzano, Italy
Chemerin is a chemotactic agonist recently identified as the ligand of ChemR23, a serpentine receptor expressed by mononuclear phagocytes and dendritic cells (DCs). This study shows that blood CD56lowCD16+ natural killer (NK) cells selectively express functional ChemR23 and that this receptor is coexpressed with CXCR1, the CXCL8 receptor, and the KIR receptors. In vitro culturing of NK cells with IL-2 or IL-15 induced a delayed and time-dependent down-regulation of ChemR23 that was associated with the inhibition of NK cell migration to chemerin. Biopsies obtained from patients with oral lichen planus presented an infiltration of CD94+CD3–CD56+ NK cells that coexpressed ChemR23. The same biopsies were infiltrated by myeloid, DC-SIGN+ and plasmacytoid, CD123+BDCA2+, ChemR23+ dendritic cells that were occasionally associated with NK cells. In the same histologic sections, chemerin was expressed by inflamed dermal endothelium. These findings propose a role for the ChemR23/chemerin axis in the recruitment of blood NK cells and strongly implicate chemerin as a key factor for the colocalization of NK cells and DC subsets in pathologic peripheral tissues.
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