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

Bain, C. C. et al. (2016) Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities. Nature Communications, 7, ncomms1185. (doi: 10.1038/ncomms11852) (PMID:27292029) (PMCID:PMC4910019)

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.

• Item Type: Articles
• Additional Information: This work was supported by the Medical Research Council (MR/L008076/1 to SJJ), MG was supported by a Marie-Curie Career Integration Grant and several FWO grants, and CLS was supported by a Marie-Curie Intra-European Fellowship. AMM received funding from the Wellcome Trust.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mowat, Professor Allan and Schridde, Ms Anika
• Authors: Bain, C. C., Hawley, C. A., Garner, H., Scott, C. L., Schridde, A., Steers, N. J., Mack, M., Joshi, A., Guilliams, M., Mowat, A., Geissmann, F., and Jenkins, S. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2016 Bain, C.C. et al.
• First Published: First published in Nature Communications 7:1185
• Publisher Policy: Reproduced under a Creative Commons License