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Immunity. 2016 Mar 15;44(3):439-449. doi: 10.1016/j.immuni.2016.02.024.

Tissue-Resident Macrophage Ontogeny and Homeostasis.

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Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China. Electronic address:
Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent 9000, Belgium. Electronic address:


Defining the origins and developmental pathways of tissue-resident macrophages should help refine our understanding of the role of these cells in various disease settings and enable the design of novel macrophage-targeted therapies. In recent years the long-held belief that macrophage populations in the adult are continuously replenished by monocytes from the bone marrow (BM) has been overturned with the advent of new techniques to dissect cellular ontogeny. The new paradigm suggests that several tissue-resident macrophage populations are seeded during waves of embryonic hematopoiesis and self-maintain independently of BM contribution during adulthood. However, the exact nature of the embryonic progenitors that give rise to adult tissue-resident macrophages is still debated, and the mechanisms enabling macrophage population maintenance in the adult are undefined. Here, we review the emergence of these concepts and discuss current controversies and future directions in macrophage biology.

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