title: Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland.
abstract: Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2-/-mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes.
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.
authors.forename: Gillian J
authors.identifier: 0000-0002-9513-8437
authors.initials: GJ
authors.lastname: Wilson
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.
authors.forename: Kay D
authors.initials: KD
authors.lastname: Hewit
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pallas
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Cairney
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.
authors.forename: Kit M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hansell
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Torsten
authors.initials: T
authors.lastname: Stein
authors.affiliation: Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK gerard.graham@glasgow.ac.uk.
authors.forename: Gerard J
authors.identifier: 0000-0002-7801-204X
authors.initials: GJ
authors.lastname: Graham
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D004622:Embryo, Mammalian; D005260:Female; D042583:Lymphangiogenesis / Q000235:genetics; D042601:Lymphatic Vessels / Q000196:embryology / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D008321:Mammary Glands, Animal / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics*; D054388:Receptors, CCR / Q000502:physiology*; D019707:Receptors, Chemokine / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: C119309:CC chemokine receptor 9; D054388:Receptors, CCR; D019707:Receptors, Chemokine
keywords: ACKR2; Branching; Chemokines; Mammary gland; Mouse