ABSTRACT
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 CD56(low)CD16(+) 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.
Subject(s)
Cell Movement/immunology , Chemokines/immunology , Dendritic Cells/immunology , Killer Cells, Natural/immunology , Lichen Planus, Oral/immunology , Receptors, Chemokine/immunology , Chemokines/biosynthesis , Dendritic Cells/metabolism , Dendritic Cells/pathology , Dermis/immunology , Dermis/metabolism , Dermis/pathology , Endothelium/immunology , Endothelium/metabolism , Endothelium/pathology , Female , Gene Expression Regulation/immunology , Humans , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Intercellular Signaling Peptides and Proteins , Interleukin-15/biosynthesis , Interleukin-15/immunology , Interleukin-2/biosynthesis , Interleukin-2/immunology , Killer Cells, Natural/metabolism , Killer Cells, Natural/pathology , Lichen Planus, Oral/metabolism , Lichen Planus, Oral/pathology , Male , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/immunology , Receptors, Chemokine/biosynthesisABSTRACT
Chemerin is a chemotactic agent that was recently identified as the ligand of ChemR23, a serpentine receptor expressed by activated macrophages and monocyte-derived dendritic cells (DCs). This paper shows that blood plasmacytoid and myeloid DCs express functional ChemR23. Recombinant chemerin induced the transmigration of plasmacytoid and myeloid DCs across an endothelial cell monolayer. In secondary lymphoid organs (lymph nodes and tonsils), ChemR23 is expressed by CD123(+) plasmacytoid DCs and by CD1a(+) DC-SIGN(+) DCs in the interfollicular T cell area. ChemR23(+) DCs were also observed in dermis from normal skin, whereas Langerhans cells were negative. Chemerin expression was selectively detected on the luminal side of high endothelial venules in secondary lymphoid organs and in dermal endothelial vessels of lupus erythematosus skin lesions. Chemerin(+) endothelial cells were surrounded by ChemR23(+) plasmacytoid DCs. Thus, ChemR23 is expressed and functional in plasmacytoid DCs, a property shared only by CXCR4 among chemotactic receptors. This finding, together with the selective expression of the cognate ligand on the luminal side of high endothelial venules and inflamed endothelium, suggests a key role of the ChemR23/chemerin axis in directing plasmacytoid DC trafficking.
