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

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

doi:10.1038/ni.3343

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.

Highlights

Ensan, Sherine, Angela Li, Rickvinder Besla, Norbert Degousee, Jake Cosme, Mark Roufaiel, Eric A Shikatani, et al 2015
Arterial macrophages were maintained by CX3CR1-CX3CL1 interactions and local proliferation without significant further contribution from blood monocytes
Here, we identified the molecular signature of arterial macrophages, their developmental pathways and key mechanisms that ensure their homeostasis

Summary

Introduction

Sherine, Angela Li, Rickvinder Besla, Norbert Degousee, Jake Cosme, Mark Roufaiel, Eric A Shikatani, et al 2015. Accumulated evidence, including recent studies using sophisticated fate-mapping approaches, have determined that some tissue macrophages and their precursors are established embryonically in the yolk sac (YS) and fetal liver before the onset of definitive hematopoiesis[4,5,6,7,8,9,10,11]. Regardless of their origin, tissue macrophages can maintain themselves in adulthood by self-renewal independent of blood monocytes[12,13]

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Results

Conclusion