Regional specialization of macrophages along the gastrointestinal tract

The tissue microenvironment is a major driver in imprinting tissue-specific macrophage functions in various mammalian tissues. As monocytes are recruited into the gastrointestinal (GI) tract at steady state and inflammation, they rapidly adopt a tissue-specific and distinct transcriptome. However, the GI tract varies significantly along its length, yet most studies of intestinal macrophages do not directly compare the phenotype and function of these macrophages in the small and large intestine, thus leading to disparities in data interpretations. This review highlights differences along the GI tract that are likely to influence macrophage function, with a specific focus on diet and microbiota. This analysis may fuel further investigation regarding the interplay between the intestinal immune system and GI tissue microenvironments, ideally providing unique therapeutic targets to modulate specific intestinal macrophage populations and/or functions.