Mast cell–expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis

Abstract

Mast cells contribute importantly to both protective and pathological IgE-dependent immune responses. We show that the mast cell–expressed orphan serpentine receptor mCCRL2 is not required for expression of IgE-mediated mast cell–dependent passive cutaneous anaphylaxis but can enhance the tissue swelling and leukocyte infiltrates associated with such reactions in mice. We further identify chemerin as a natural nonsignaling protein ligand for both human and mouse CCRL2. In contrast to other “silent” or professional chemokine interreceptors, chemerin binding does not trigger ligand internalization. Rather, CCRL2 is able to bind the chemoattractant and increase local concentrations of bioactive chemerin, thus providing a link between CCRL2 expression and inflammation via the cell-signaling chemerin receptor CMKLR1.

Trafficking properties of plasmacytoid dendritic cells in health and disease

“…Therefore, ChemR23 may also possess anti-inflammatory activities, as recently suggested in experiments testing a mouse model of lung inflammation [96]. CCRL2, an orphan serpentine receptor binds chemerin at the N-terminal in the absence of receptor signalling and internalization, and presents chemerin to ChemR23-positive cells in vitro [56]. This finding discloses a new potential role of chemerin in leukocyte recruitment.…”

“…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].…”

Differential Patterns of Serum Concentration and Adipose Tissue Expression of Chemerin in Obesity: Adipose Depot Specificity and Gender Dimorphism

“…Chemerin, a recently discovered circulating chemokine, exerts its actions through cell surface receptors termed chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), or chemokine (C-C motif) receptor-like 2 (CCRL2) (Barnea et al, 2008;Cash et al, 2008;Wittamer et al, 2003;Zabel et al, 2008). Later studies characterized chemerin as an adipokine with a potential role in regulating adipocyte development in vitro and metabolic functions, such as glucose and lipid metabolism, in adipose tissue (Goralski et al, 2007).…”

La chémérine

“…Dans des cellules HEK (human embryonic kidney) 293T transfectées avec le récepteur GPR1, la fixation de la chémérine S157 entraîne une faible mobilisation calcique [16]. Enfin, CCRL2 n'induit pas de signalisation intracellulaire connue à ce jour [17,18]. Ce récepteur est fortement exprimé dans les cellules endothéliales du poumon et plus faiblement au niveau du foie [19].…”

“…Ce récepteur est fortement exprimé dans les cellules endothéliales du poumon et plus faiblement au niveau du foie [19]. Il pourrait réguler la biodisponibilité de la chémérine en la séquestrant et en la présentant au récepteur CMKLR1 présent sur des cellules voisines [18].…”