Nat Rev Gastroenterol Hepatol. 2023 Aug;20(8):538-553.doi: 10.1038/s41575-023-00769-0. Epub 2023 Apr 17.

Lizi M Hegarty ^# 1, Gareth-Rhys Jones ^# 1, Calum C Bain ²

Author information

¹Centre for Inflammation Research, Institute of Regeneration and Repair, University of Edinburgh, Edinburgh BioQuarter, Queen's Medical Research Institute, Edinburgh, UK.

²Centre for Inflammation Research, Institute of Regeneration and Repair, University of Edinburgh, Edinburgh BioQuarter, Queen's Medical Research Institute, Edinburgh, UK. calum.bain@ed.ac.uk.

^#Contributed equally.

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.