1. Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth
- Author
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Cedric C. Li, Barry B. Rubin, Peter Wieghofer, Clinton S. Robbins, Lauren Robins, Peter Libby, Gwendalyn J. Randolph, Kaveh Farrokhi, Anthony O. Gramolini, Norbert Degousee, Maral Ouzounian, Carla M. T. Bauer, Mansoor Husain, Bonnie Lewis, Mahmoud El-Maklizi, Jun Seong Lee, Eric A. Shikatani, Jesse W. Williams, Angela Li, Tae Jin Yun, Slava Epelman, Filip K. Swirski, Cheolho Cheong, Rickvinder Besla, Mark Roufaiel, Caleb C. J. Zavitz, Jake Cosme, Ramzi Khattar, Marco Prinz, Myron I. Cybulsky, Gary A. Levy, Ingo Hilgendorf, Sherine Ensan, and John Byrne
- Subjects
Male ,0301 basic medicine ,Cell Survival ,Immunology ,Population ,CX3C Chemokine Receptor 1 ,Mice, Transgenic ,Inflammation ,Biology ,Monocytes ,Immunophenotyping ,Sepsis ,Mice ,03 medical and health sciences ,CX3CR1 ,medicine ,Animals ,Cluster Analysis ,Immunology and Allergy ,Cell Self Renewal ,Stem Cell Niche ,education ,Receptor ,Embryonic Stem Cells ,education.field_of_study ,Chemokine CX3CL1 ,Gene Expression Profiling ,Macrophages ,Monocyte ,medicine.disease ,Embryonic stem cell ,Cell biology ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,Female ,Receptors, Chemokine ,medicine.symptom ,Transcriptome ,Homeostasis ,Protein Binding - 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.
- Published
- 2015
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