Key Points
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Most tissue-resident macrophages arise from embryonic precursors that are recruited to the tissues before birth and can be maintained locally, independently of circulating precursors.
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Macrophage functional identity is dictated by tissue-derived factors but may also be partly determined by their origin.
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Macrophage–tissue crosstalk contributes to tissue homeostasis and repair.
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Circulating monocytes give rise to monocyte-derived cells in inflamed and tumour tissues, but it is unclear whether monocyte-derived cells persist in tissues once inflammation resolves.
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The exact contribution of monocyte-derived and tissue-resident macrophages to tumour progression remains to be established.
Abstract
Macrophages are immune cells of haematopoietic origin that provide crucial innate immune defence and have tissue-specific functions in the regulation and maintenance of organ homeostasis. Recent studies of macrophage ontogeny, as well as transcriptional and epigenetic identity, have started to reveal the decisive role of the tissue stroma in the regulation of macrophage function. These findings suggest that most macrophages seed the tissues during embryonic development and functionally specialize in response to cytokines and metabolites that are released by the stroma and drive the expression of unique transcription factors. In this Review, we discuss how recent insights into macrophage ontogeny and macrophage–stroma interactions contribute to our understanding of the crosstalk that shapes macrophage function and the maintenance of organ integrity.
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Acknowledgements
The authors thank M. Acebes-Casanova, V. Kana and A. Chudnovsky for critical review of the manuscript. This work was supported by the following grants awarded to M.M.: R01CA154947A, R01CA190400, R01CA173861, U01AI095611 and R01AI104848.
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FURTHER INFORMATION
Glossary
- Mononuclear phagocyte system
-
(MPS). A group of bone marrow-derived cells (monocytes, macrophages and dendritic cells) with different morphologies. These cells are mainly responsible for phagocytosis, cytokine secretion and antigen presentation.
- Parabiotic mice
-
Mice in which the blood circulation has been joined surgically. Parabiotic mice share the same blood circulation and exchange blood precursor cells, thereby providing a model to trace the physiological contribution of circulating precursors to tissue-resident cells.
- B-1 cells
-
An innate-like population of B cells found mainly in the peritoneal and pleural cavities. B-1 cell precursors develop in the fetal liver and omentum. B-1 cells recognize self-antigens as well as common bacterial antigens and secrete antibodies of low affinity and broad specificity.
- Omentum
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A fatty tissue in the peritoneum that connects the spleen, stomach, pancreas and colon.
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Lavin, Y., Mortha, A., Rahman, A. et al. Regulation of macrophage development and function in peripheral tissues. Nat Rev Immunol 15, 731–744 (2015). https://doi.org/10.1038/nri3920
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DOI: https://doi.org/10.1038/nri3920
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