Increased inflammation in mice deficient for the chemokine decoy receptor D6.
Chemokines are chemotactic cytokines with a key role in the control of cell trafficking and positioning under homeostatic and inflammatory conditions. D6 is a promiscuous 7-transmembrane-domain receptor expressed on lymphatic vessels which recognizes most inflammatory, but not homeostatic, CC chemokines. In vitro experiments demonstrated that D6 is unable to signal after ligand engagement, and it is structurally adapted to sustain rapid and efficient ligand internalization and degradation. These unique functional properties lead to the hypothesis that D6 may be involved in the control of inflammation by acting as a decoy and scavenger receptor for inflammatory chemokines. Consistent with this hypothesis, here we report that D6(-/-) mice showed an anticipated and exacerbated inflammatory response in a model of skin inflammation. Moreover, the absence of D6 resulted in increase cellularity and inflammatory-chemokine levels in draining lymph nodes. Thus, D6 is a decoy receptor structurally adapted and strategically located to tune tissue inflammation and control transfer of inflammatory chemokines to draining lymph nodes.
Martinez de la Torre
Yeny
Y
Institute of General Pathology, Medical Faculty, University of Milan, Milan, Italy.
Locati
Massimo
M
Buracchi
Chiara
C
Dupor
Jana
J
Cook
Donald N
DN
Bonecchi
Raffaella
R
Nebuloni
Manuela
M
Rukavina
Daniel
D
Vago
Luca
L
Vecchi
Annunciata
A
Lira
Sergio A
SA
Mantovani
Alberto
A
D000818:Animals; D007249:Inflammation / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000276:immunology; D012867:Skin / Q000276:immunology; D000097628:Chemokine Receptor D6
D054447:Receptors, CCR10; D019707:Receptors, Chemokine; D000097628:Chemokine Receptor D6