Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin

Abstract

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.

Trafficking properties of plasmacytoid dendritic cells in health and disease

“…However, the mechanisms underlying this effect are elusive. Recently, we and others have characterized chemerin, the ligand of ChemR23, as a new chemotactic factor for PDCs (Box 1) [55,56]. Chemerin is expressed by HEV in reactive lymph nodes and by activated dermal blood vessels in autoimmune skin lesions [55,57,58].…”

“…Conversely, in other skin diseases, such as atopic dermatitis, PDCs are not recruited to the inflamed tissue [53]. In LE and psoriasis, cutaneous accumulation of PDCs is associated with the local activation of the chemerin/ChemR23 axis (Box 1) [55,57,63]. In particular, chemerin is strongly induced in keratinocytes, dermal vessels and fibroblasts, whereas skin infiltrating PDCs strongly express ChemR23.…”

“…ChemR23 is expressed by antigenpresenting cells, such as MDCs, PDCs and macrophages, and by blood monocytes and NK cells [55,58,92]. In contrast to other chemotactic receptors, human ChemR23 maps to chromosome 12, and shows little homology with other receptors of the same family (e.g.…”

“…In vivo, ChemR23 is expressed in the lymph node by interfollicular MDCs and PDCs, by sinus macrophages and by germinal center macrophages. In inflamed skin, ChemR23 expression is mostly restricted to MDCs and PDCs [55]. Chemerin, the only natural ligand so far identified for this receptor, was originally purified from ovarian cancer ascites and rheumatoid synovial fluids, and corresponds to the product of the Tig-2 gene.…”

ChemR23, the Receptor for Chemerin and Resolvin E1, Is Expressed and Functional on M1 but Not on M2 Macrophages

“…It binds two ligands: the peptide chemerin (12) and the eicosapentaenoic acid-derived lipid mediator 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid named resolvin E1 (RvE1) (13,14). Chemerin is present in high amounts in inflammatory fluids (15), has antimicrobial activities (16), was shown to attract ChemR23-expressing leukocytes (12,17), and promotes adhesion of macrophages to extracellular matrix proteins (18). In addition, chemerin was recently discovered to be an adipokine (10).…”