title: Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and regulated by GATA1.
abstract: D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes.
authors.affiliation: Division of Immunology, Grasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Clive S
authors.initials: CS
authors.lastname: McKimmie
authors.forename: Alasdair R
authors.initials: AR
authors.lastname: Fraser
authors.forename: Chris
authors.initials: C
authors.lastname: Hansell
authors.forename: Laura
authors.initials: L
authors.lastname: Gutiérrez
authors.forename: Sjaak
authors.initials: S
authors.lastname: Philipsen
authors.forename: Laura
authors.initials: L
authors.lastname: Connell
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.forename: Mariola
authors.initials: M
authors.lastname: Kurowska-Stolarska
authors.forename: Paz
authors.initials: P
authors.lastname: Carreno
authors.forename: Monika
authors.initials: M
authors.lastname: Pruenster
authors.forename: Ching-Chung
authors.initials: CC
authors.lastname: Chu
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Christina
authors.initials: C
authors.lastname: Halsey
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nibbs
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D054447:Receptors, CCR10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology; D000097628:Chemokine Receptor D6
chemical_list: D018925:Chemokines; D050982:GATA1 Transcription Factor; D008070:Lipopolysaccharides; D054447:Receptors, CCR10; D016212:Transforming Growth Factor beta; D000097628:Chemokine Receptor D6; C494688:GATA1 protein, human