Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309.
The human CC chemokine I-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines. Here, we identify a specific human I-309 receptor, and name it CCR8 according to an accepted nomenclature system. The receptor has seven predicted transmembrane domains, is expressed constitutively in monocytes and thymus, and is encoded by a previously reported gene of previously unknown function named, alternatively, CY6, TER1, and CKR-L1. After transfection with the CY6 open reading frame, a mouse pre-B cell line exhibited calcium flux and chemotaxis in response to I-309 (EC50 = 2 nM for each), whereas 20 other chemokines were inactive. Signaling was sensitive to pertussis toxin, suggesting coupling to a Gi-type G protein. These properties parallel those of endogenous I-309 receptors expressed in an HL-60 clone 15 cell line model. The apparent monogamous relationship between I-309 and CCR8 is unusual among known CC chemokines and known CC chemokine receptors. CCR8 may regulate monocyte chemotaxis and thymic cell line apoptosis.
Tiffany
H L
HL
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lautens
L L
LL
Gao
J L
JL
Pease
J
J
Locati
M
M
Combadiere
C
C
Modi
W
W
Bonner
T I
TI
Murphy
P M
PM
D000818:Animals; D054402:Chemokine CCL1; D019742:Chemokines, CC; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000032:analysis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism*
C065971:CCL1 protein, human; C103330:CCR8 protein, human; C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D019742:Chemokines, CC; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine