Abstract
Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying cells and cell debris, immune complexes, bacteria and other waste products. Simultaneously, they produce growth factors and signalling molecules — such activities not only promote host protection in response to invading microorganisms but are also crucial for organ development and homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, such as blood vessel formation, adipogenesis, metabolism and central and peripheral neuronal function. In parallel, novel methodologies have led to the characterization of tissue-specific macrophages, with distinct subpopulations of these cells showing different developmental trajectories, transcriptional programmes and life cycles. Here, we summarize our growing knowledge of macrophage diversity and how macrophage subsets orchestrate tissue development and function. We further interrelate macrophage ontogeny with their core functions across tissues, that is, the signalling events within the macrophage niche that may control organ functionality during development, homeostasis and ageing. Finally, we highlight the open questions that will need to be addressed by future studies to better understand the tissue-specific functions of distinct macrophage subsets.
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Acknowledgements
The authors thank all their laboratory members for their ambitious work and passionate research on myeloid cells. The authors apologize to all colleagues, whose work could not be cited in this work owing to space limitations. E.M. and A.S. are supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy — EXC 2151 — 390873048. E.M. is supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 851257) and by the DFG Grant SFB1454 (projects INST 217/1042-1 and INST 217/1037-1). F.N. is supported by the Deutsche Forschungsgemeinschaft (CRC 1181-A07, CRC1526-A07, TRR305-B02, FOR2953-P3, FOR2886-P2) and the NIH (U19 AI142790, RFA-AI-18-042). K.K. is supported by a project grant of the Fritz Thyssen Foundation and the German Research Foundation (DFG) by project grants within the SFB/TRR167 (Project ID 259373024), the CRC1479 (Project ID 44189134), the SFB/TRR359 (Project ID 491676693) and by the DFG under Germany’s Excellence Strategy (Grant No. CIBSS — EXC-2189, Project ID 390939984). A.S. is supported by an Emmy Noether Research Grant (SCHL2116/1), DFG Research Grants (SCHL2116/6-1 and SCHL2116/7-1), the GRK214362475/GRK1873/2 and the DFG CRC1454 (Project INST 217/1042-1).
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Glossary
- 12-Hydroxyeicosatetraenoic acid
-
A pro-inflammatory eicosanoid metabolite produced by cells.
- Erythroblastic island
-
(EBI). A cluster of developing red blood cells forming around a central macrophage that supports their maturation.
- Hepatic stellate cells
-
Also known as vitamin A and lipid-storing cells, located between the endothelial lining and hepatocytes contributing to liver homeostasis via autocrine, paracrine and chemoattractant factors.
- Hofbauer cells
-
Placental macrophages that are present throughout pregnancy.
- Human Cell Atlas
-
A large-scale, international effort aimed at mapping the diversity and distribution of cells in the human body.
- Kolmer epiplexus cells
-
Intraventricular tissue-resident macrophage population associated with the multiciliated cuboid ependymal cells of the choroid plexus in all ventricles.
- Type II airway epithelial cells
-
Specialized cells in the respiratory system responsible for the production of surfactant.
- Virchow-Robin/perivascular space
-
Space surrounding blood vessels within tissues, filled with perivascular cells and the extracellular fluid.
- Wildlings
-
C57BL/6 mice that are colonized by natural microbiota and pathogens at all body sites.
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Mass, E., Nimmerjahn, F., Kierdorf, K. et al. Tissue-specific macrophages: how they develop and choreograph tissue biology. Nat Rev Immunol 23, 563–579 (2023). https://doi.org/10.1038/s41577-023-00848-y
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DOI: https://doi.org/10.1038/s41577-023-00848-y
