Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities

Calum C. Bain, Catherine A. Hawley, Hannah Garner, Charlotte L. Scott, Anika Schridde, Nicholas J. Steers, Matthias Mack, Anagha Joshi, Martin Guilliams, Allan Mc I. Mowat, Frederic Geissmann and Stephen J. Jenkins ()
Additional contact information
Calum C. Bain: The University of Edinburgh/MRC Centre for Inflammation Research, Queens Medical Research Institute
Catherine A. Hawley: The University of Edinburgh/MRC Centre for Inflammation Research, Queens Medical Research Institute
Hannah Garner: Centre for Molecular and Cellular Biology of Inflammation (CMCBI)
Charlotte L. Scott: Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center
Anika Schridde: Institute of Infection, Immunity and Inflammation, University of Glasgow
Nicholas J. Steers: The University of Edinburgh/MRC Centre for Inflammation Research, Queens Medical Research Institute
Matthias Mack: Department of Internal Medicine - Nephrology University Hospital Regensburg
Anagha Joshi: The Roslin Institute and Royal (Dick) School of Veterinary Studies, Easter Bush Campus, University of Edinburgh
Martin Guilliams: Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center
Allan Mc I. Mowat: Institute of Infection, Immunity and Inflammation, University of Glasgow
Frederic Geissmann: Centre for Molecular and Cellular Biology of Inflammation (CMCBI)
Stephen J. Jenkins: The University of Edinburgh/MRC Centre for Inflammation Research, Queens Medical Research Institute

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Peritoneal macrophages are one of the most studied macrophage populations in the body, yet the composition, developmental origin and mechanisms governing the maintenance of this compartment are controversial. Here we show resident F4/80hiGATA6+ macrophages are long-lived, undergo non-stochastic self-renewal and retain cells of embryonic origin for at least 4 months in mice. However, Ly6C+ monocytes constitutively enter the peritoneal cavity in a CCR2-dependent manner, where they mature into short-lived F4/80loMHCII+ cells that act, in part, as precursors of F4/80hiGATA6+ macrophages. Notably, monocyte-derived F4/80hi macrophages eventually displace the embryonic population with age in a process that is highly gender dependent and not due to proliferative exhaustion of the incumbent embryonic population, despite the greater proliferative activity of newly recruited cells. Furthermore, although monocyte-derived cells acquire key characteristics of the embryonic population, expression of Tim4 was impaired, leading to cumulative changes in the population with age.

Date: 2016
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DOI: 10.1038/ncomms11852

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