Abstract
Macrophages are essential for the maintenance of intestinal homeostasis, yet appear to be drivers of inflammation in the context of inflammatory bowel disease (IBD). How these peacekeepers become powerful aggressors in IBD is still unclear, but technological advances have revolutionized our understanding of many facets of their biology. In this Review, we discuss the progress made in understanding the heterogeneity of intestinal macrophages, the functions they perform in gut health and how the environment and origin can control the differentiation and longevity of these cells. We describe how these processes might change in the context of chronic inflammation and how aberrant macrophage behaviour contributes to IBD pathology, and discuss how therapeutic approaches might target dysregulated macrophages to dampen inflammation and promote mucosal healing. Finally, we set out key areas in the field of intestinal macrophage biology for which further investigation is warranted.
Key points
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Advances in single-cell RNA sequencing and fate-mapping mouse models have uncovered the heterogeneity of intestinal macrophages.
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Intestinal macrophage subsets in discrete niches have distinct functions and replenishment kinetics from monocytes.
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Dysregulated monocytes and macrophages are a characteristic feature of intestinal inflammation.
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The environmental signals and downstream molecular pathways governing monocyte-to-macrophage differentiation in health and how these change in inflammation remain poorly understood.
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Understanding the molecular dialogue between macrophage subsets and other immune cells and their niche will enable macrophage dysfunction to be targeted in inflammatory bowel disease.
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Acknowledgements
All authors are funded by the Wellcome Trust/Royal Society in the form of a PhD studentship (L.M.H.; 222356/Z/21/Z), Clinical Career Development Fellowship (G.-R.J.; 220725/Z/20/Z) and a Sir Henry Dale Fellowship (C.C.B.; 206234/Z/17/Z).
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Hegarty, L.M., Jones, GR. & Bain, C.C. Macrophages in intestinal homeostasis and inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 20, 538–553 (2023). https://doi.org/10.1038/s41575-023-00769-0
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DOI: https://doi.org/10.1038/s41575-023-00769-0
