Abstract
Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate from early yolk sac progenitors and are specified into tissue-specific subsets during organogenesisâestablishing stable spatial and functional relationships with specialized tissue cellsâand persist in adults. Resident macrophages are an integral part of tissues together with specialized cells: for instance, microglia reside with neurons in brain, osteoclasts reside with osteoblasts in bone, and fat-associated macrophages reside with white adipocytes in adipose tissue. This ancillary cell type, which is developmentally and functionally distinct from haematopoietic stem cell and monocyte-derived macrophages, senses and integrates local and systemic information to provide specialized tissue cells with the growth factors, nutrient recycling and waste removal that are critical for tissue growth, homeostasis and repair. Resident macrophages contribute to organogenesis, promote tissue regeneration following damage and contribute to tissue metabolism and defence against infectious disease. A correlate is that genetic or environment-driven resident macrophage dysfunction is a cause of degenerative, metabolic and possibly inflammatory and tumoural diseases. In this Review, we aim to provide a conceptual outline of our current understanding of macrophage physiology and its importance in human diseases, which may inform and serve the design of future studies.
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Change history
03 July 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41586-023-06386-w
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Acknowledgements
The authors acknowledge present and past members of the Geissmann laboratory, researchers at Memorial Sloan Kettering Cancer Center (MSKCC), and the scientific community at large for scientific discussions. This work was supported by NIH/NCI P30CA008748 to MSKCC and by NIH/NIAID 1R01AI130345, NIH/NHLBI R01HL138090, NIH R01 NS115715-03, Leducq transatlantic network of excellence and Ludwig institute for Cancer research basic immunology grant to F.G. and NIH/NIDDK K99 DK131280 to N.C. S.J.-C. is a CRI Irvington postdoctoral fellow.
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Lazarov, T., Juarez-Carreño, S., Cox, N. et al. Physiology and diseases of tissue-resident macrophages. Nature 618, 698â707 (2023). https://doi.org/10.1038/s41586-023-06002-x
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DOI: https://doi.org/10.1038/s41586-023-06002-x
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