Self-renewing resident arterial macrophages arise from embryonic CX3CR1 + precursors and circulating monocytes immediately after birth

Sherine Ensan, Angela Li, Rickvinder Besla, Norbert Degousee, Jake Cosme, Mark Roufaiel, Eric A. Shikatani, Mahmoud El-Maklizi, Jesse W. Williams, Lauren Robins, Cedric Li, Bonnie Lewis, Tae Jin Yun, Jun Seong Lee, Peter Wieghofer, Ramzi Khattar, Kaveh Farrokhi, John Byrne, Maral Ouzounian, Caleb C.J. ZavitzGary A. Levy, Carla M.T. Bauer, Peter Libby, Mansoor Husain, Filip K. Swirski, Cheolho Cheong, Marco Prinz, Ingo Hilgendorf, Gwendalyn J. Randolph, Slava Epelman, Anthony O. Gramolini, Myron I. Cybulsky, Barry B. Rubin, Clinton S. Robbins

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)159-168
Number of pages10
JournalNature immunology
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2016

Bibliographical note

Funding Information:
We acknowledge the administrative assistance of B. Bali. Supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award (MSH136670), a CIHR operating grant (MOP133390), an Ontario Lung Association/Pfizer Award and the Peter Munk Chair in Aortic Disease Research (C.S.R.) and an Ontario Graduate Scholarship (S.E.).

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