title: Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth.
abstract: Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1(+) precursors and postnatally from bone marrow-derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sherine
authors.initials: S
authors.lastname: Ensan
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Angela
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rickvinder
authors.initials: R
authors.lastname: Besla
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Norbert
authors.initials: N
authors.lastname: Degousee
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Jake
authors.initials: J
authors.lastname: Cosme
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Mark
authors.identifier: http://orcid.org/0000-0003-4174-1043
authors.initials: M
authors.lastname: Roufaiel
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Shikatani
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: El-Maklizi
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Jesse W
authors.initials: JW
authors.lastname: Williams
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Robins
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Li
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Lewis
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, Quebec, Canada.
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Yun
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, Quebec, Canada.
authors.forename: Jun Seong
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Institute of Neuropathology and Faculty of Biology, University of Freiburg, Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wieghofer
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Khattar
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Farrokhi
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Byrne
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Maral
authors.initials: M
authors.lastname: Ouzounian
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Caleb C J
authors.initials: CC
authors.lastname: Zavitz
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Levy
authors.affiliation: Hoffmann-La Roche, pRED, Pharma Research and Early Development, DTA Inflammation, Nutley, New Jersey, USA.
authors.forename: Carla M T
authors.initials: CM
authors.lastname: Bauer
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.|Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Husain
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston,MA, USA.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, Quebec, Canada.
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
authors.affiliation: Institute of Neuropathology and BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.affiliation: Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Hilgendorf
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Slava
authors.initials: S
authors.lastname: Epelman
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Anthony O
authors.initials: AO
authors.lastname: Gramolini
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.|Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Myron I
authors.initials: MI
authors.lastname: Cybulsky
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Barry B
authors.initials: BB
authors.lastname: Rubin
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.|Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Robbins
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D000066673:Cell Self Renewal; D002470:Cell Survival; D054428:Chemokine CX3CL1 / Q000378:metabolism; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000378:metabolism*; D055153:Stem Cell Niche; D059467:Transcriptome
chemical_list: D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine