Differential recognition and scavenging of native and truncated macrophage-derived chemokine (macrophage-derived chemokine/CC chemokine ligand 22) by the D6 decoy receptor.
The promiscuous D6 receptor binds several inflammatory CC chemokines and has been recently proposed to act as a chemokine-scavenging decoy receptor. The present study was designed to better characterize the spectrum of CC chemokines scavenged by D6, focusing in particular on CCR4 ligands and analyzing the influence of NH(2)-terminal processing on recognition by this promiscuous receptor. Using D6 transfectants, it was found that D6 efficiently bound and scavenged most inflammatory CC chemokines (CCR1 through CCR5 agonists). Homeostatic CC chemokines (CCR6 and CCR7 agonists) were not recognized by D6. The CCR4 agonists CC chemokine ligand 17 (CCL17) and CCL22 bound to D6 with high affinity. CCL17 and CCL22 have no agonistic activity for D6 (chemotaxis and calcium fluxes), but were rapidly scavenged, resulting in reduced chemotactic activity on CCR4 transfectants. CD26 mediates NH(2) terminus processing of CCL22, leading to the production of CCL22 (3-69) and CCL22 (5-69) that do not interact with CCR4. These NH(2)-terminal truncated forms of CCL22 were not recognized by D6. The results presented in this study show that D6 recognizes and scavenges a wide spectrum of inflammatory CC chemokines, including the CCR4 agonists CCL22 and CCL17. However, this promiscuous receptor is not engaged by CD26-processed, inactive, CCL22 variants. By recognizing intact CCL22, but not its truncated variants, D6 expressed on lymphatic endothelial cells may regulate the traffic of CCR4-expressing cells, such as dendritic cells.
Bonecchi
Raffaella
R
Department of Biomedical Sciences and Biotechnology, Section of General Pathology and Immunology, University of Brescia, Brescia, Italy.
Locati
Massimo
M
Galliera
Emanuela
E
Vulcano
Marisa
M
Sironi
Marina
M
Fra
Anna M
AM
Gobbi
Marco
M
Vecchi
Annunciata
A
Sozzani
Silvano
S
Haribabu
Bodduluri
B
Van Damme
Jo
J
Mantovani
Alberto
A
D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000378:metabolism* / Q000502:physiology; D002999:Clone Cells; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology; D004729:Endothelium, Lymphatic / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D017384:Sequence Deletion; D014162:Transfection; D000097628:Chemokine Receptor D6
D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D018819:Dipeptidyl Peptidase 4; D020033:Protein Isoforms; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D000097628:Chemokine Receptor D6; C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; C499538:Ccl17 protein, mouse; C515483:Ccl22 protein, mouse; C515355:Ccr4 protein, mouse