Abstract
Macrophages are increasingly recognized as essential players in the maintenance of intestinal homeostasis and as key sentinels of the intestinal immune system. However, somewhat paradoxically, they are also implicated in chronic pathologies of the gastrointestinal tract, such as inflammatory bowel disease (IBD) and are therefore considered potential targets for novel therapies. In this review, we will discuss recent advances in our understanding of intestinal macrophage heterogeneity, their ontogeny and the potential factors that regulate their origin. We will describe how the local environment of the intestine imprints the phenotypic and functional identity of the macrophage compartment, and how this changes during intestinal inflammation and infection. Finally, we highlight key outstanding questions that should be the focus of future research.
Highlights
The gastrointestinal tract faces an unrivaled exposure to foreign antigens and, as a result, is home to the largest compartment of the immune system
We will first discuss the current understanding of macrophage heterogeneity in the gut wall, before describing the roles macrophages play in intestinal homeostasis and how this may depend on their anatomical positioning
We will review the recent developments in intestinal macrophage ontogeny, discussing how the local environment of the gut imprints the phenotypic and functional identity of macrophages, before describing the changes that occur when homeostasis is perturbed by inflammation
Summary
The gastrointestinal tract faces an unrivaled exposure to foreign antigens and, as a result, is home to the largest compartment of the immune system This includes a network of mononuclear phagocytes (MPs), including macrophages and conventional dendritic cells (cDCs), that play distinct yet complementary roles in discriminating between innocuous antigens and potential pathogens, ensuring that the appropriate response is mounted to each. While this is a highly efficient process, it can break down in some individuals, leading to the development of chronic inflammation, such as inflammatory bowel disease (IBD) in which inappropriate immune responses are mounted against the commensal microbiota. We will review the recent developments in intestinal macrophage ontogeny, discussing how the local environment of the gut imprints the phenotypic and functional identity of macrophages, before describing the changes that occur when homeostasis is perturbed by inflammation
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