title: Increased inflammation in mice deficient for the chemokine decoy receptor D6.
abstract: 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.
authors.affiliation: Institute of General Pathology, Medical Faculty, University of Milan, Milan, Italy.
authors.forename: Yeny
authors.initials: Y
authors.lastname: Martinez de la Torre
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.forename: Chiara
authors.initials: C
authors.lastname: Buracchi
authors.forename: Jana
authors.initials: J
authors.lastname: Dupor
authors.forename: Donald N
authors.initials: DN
authors.lastname: Cook
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bonecchi
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Daniel
authors.initials: D
authors.lastname: Rukavina
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.forename: Annunciata
authors.initials: A
authors.lastname: Vecchi
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: 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
chemical_list: D054447:Receptors, CCR10; D019707:Receptors, Chemokine; D000097628:Chemokine Receptor D6