The CD200 receptor is a novel and potent regulator of murine and human mast cell function.
CD200R is a member of the Ig supergene family that is primarily expressed on myeloid cells. Recent in vivo studies have suggested that CD200R is an inhibitory receptor capable of regulating the activation threshold of inflammatory immune responses. Here we provide definitive evidence that CD200R is expressed on mouse and human mast cells and that engagement of CD200R by agonist Abs or ligand results in a potent inhibition of mast cell degranulation and cytokine secretion responses. CD200R-mediated inhibition of FcepsilonRI activation was observed both in vitro and in vivo and did not require the coligation of CD200R to FcepsilonRI. Unlike the majority of myeloid inhibitory receptors, CD200R does not contain a phosphatase recruiting inhibitory motif (ITIM); therefore, we conclude that CD200R represents a novel and potent inhibitory receptor that can be targeted in vivo to regulate mast cell-dependent pathologies.
Cherwinski
Holly M
HM
DNAX Research Institute, Palo Alto, CA 94304, USA.
Murphy
Craig A
CA
Joyce
Barbara L
BL
Bigler
Mike E
ME
Song
Yaoli S
YS
Zurawski
Sandra M
SM
Moshrefi
Mehrdad M
MM
Gorman
Daniel M
DM
Miller
Kathy L
KL
Zhang
Shuli
S
Sedgwick
Jonathan D
JD
Phillips
Joseph H
JH
D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000954:Antigens, Surface; C492346:CD200 receptor, mouse; C477337:CD200R1 protein, human; C501103:Cd200r1 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D017455:Receptors, IgE; C042739:antigens, CD200