title: Cell-autonomous regulation of neutrophil migration by the D6 chemokine decoy receptor.
abstract: Chemokines, acting on their cognate receptors on infiltrating leukocytes, drive the inflammatory response. We have been interested in determining roles and potential mechanisms for the atypical chemokine-scavenging receptor D6 in the regulation of inflammation. In this study, we show that a psoriasis-like pathology that arises in inflamed skins of D6-deficient mice is characterized by a massive and aberrant localization of neutrophils to the dermal/epidermal junction, which is associated with development of the pathology. Such misplacement of neutrophils is also seen with D6-deficient mice in other inflammatory models, suggesting a role for D6 in the spatial positioning of neutrophils within inflamed sites. We further show that D6 functions cell autonomously in this context and that D6, expressed by neutrophils, limits their migrational responses to CCR1 ligands such as CCL3. Our data therefore indicate that D6 is able to play a cell-autonomous role as a migratory rheostat restricting migration of D6-expressing cells such as neutrophils toward ligands for coexpressed inflammatory chemokine receptors. These data have important implications for our understanding of the roles for D6 in regulating inflammation and for our understanding of the control of spatial positioning of leukocytes at inflamed sites.
authors.affiliation: NIBR, Brunnerstrasse 59, Vienna A1235, Austria.|MRC Centre for Immune Regulation, University of Birmingham, Birmingham, B15 2TT, UK.
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: McKimmie
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Burt
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pallas
authors.affiliation: Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow, G61 1BD, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jamieson
authors.affiliation: NIBR, Brunnerstrasse 59, Vienna A1235, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Pruenster
authors.affiliation: Berlex Biosciences 2600 Hilltop Drive, Richmond, CA 94806, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Horuk
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Robert J B
authors.initials: RJB
authors.lastname: Nibbs
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007154:Immune System Diseases / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007960:Leukocyte Disorders / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D019707:Receptors, Chemokine / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D000097628:Chemokine Receptor D6
chemical_list: D019707:Receptors, Chemokine; C515709:Ackr2 protein, mouse; D000097628:Chemokine Receptor D6