Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis.
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.
Zabel
Brian A
BA
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. bazabel@alum.mit.edu
Nakae
Susumu
S
Zúñiga
Luis
L
Kim
Ji-Yun
JY
Ohyama
Takao
T
Alt
Carsten
C
Pan
Junliang
J
Suto
Hajime
H
Soler
Dulce
D
Allen
Samantha J
SJ
Handel
Tracy M
TM
Song
Chang Ho
CH
Galli
Stephen J
SJ
Butcher
Eugene C
EC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D054388:Receptors, CCR / Q000235:genetics / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
D000911:Antibodies, Monoclonal; C487531:CCRL2 protein, human; C111851:Ccrl2 protein, mouse; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D007073:Immunoglobulin E
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