Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities.
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 F4/80(hi)GATA6(+) 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 F4/80(lo)MHCII(+) cells that act, in part, as precursors of F4/80(hi)GATA6(+) macrophages. Notably, monocyte-derived F4/80(hi) 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.
The University of Edinburgh/MRC Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Calum C
CC
Bain
The University of Edinburgh/MRC Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Catherine A
CA
Hawley
Centre for Molecular and Cellular Biology of Inflammation (CMCBI), New Hunt's House, King's College London, Great Maze Pond, London SE1 1UL, UK.
Hannah
H
Garner
Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9000, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent 9000, Belgium.
Charlotte L
CL
Scott
Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.|Institute of Molecular Medicine, RWTH University, 52074 Aachen, Germany.
Anika
A
Schridde
The University of Edinburgh/MRC Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Nicholas J
NJ
Steers
Department of Internal Medicine - Nephrology University Hospital Regensburg, Regensburg 93042, Germany.
Matthias
M
Mack
The Roslin Institute and Royal (Dick) School of Veterinary Studies, Easter Bush Campus, University of Edinburgh, Midlothian EH25 9RG, UK.
Anagha
A
Joshi
Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9000, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent 9000, Belgium.
Martin
0000-0003-3525-7570
M
Guilliams
Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Allan Mc I
AM
Mowat
Centre for Molecular and Cellular Biology of Inflammation (CMCBI), New Hunt's House, King's College London, Great Maze Pond, London SE1 1UL, UK.|Immunology Program, Memorial Sloan Kettering Cancer Center, 417 East 68th Street, New York, New York 10065, USA.|Weill Cornell Graduate School of Medical Sciences, New York, New York 10065, USA.
Frederic
F
Geissmann
The University of Edinburgh/MRC Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Stephen J
SJ
Jenkins
D000375:Aging / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D004622:Embryo, Mammalian / Q000166:cytology*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology; D010641:Phenotype; D054390:Receptors, CCR2 / Q000378:metabolism; D013997:Time Factors
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2