Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD

• Published in: Nature reviews. Gastroenterology & hepatology 2019-09, Vol.16 (9), p.531-543
• Main Authors: Na, Yi Rang, Stakenborg, Michelle, Seok, Seung Hyeok, Matteoli, Gianluca
• Format: Article
• Language: English
• Subjects: 692/4020/1503/1581/257; 692/420/256; 692/698/2741; 692/698/690/292; Antigens; Biomedicine; Care and treatment; Development and progression; Gastroenterology; Gastrointestinal Microbiome - immunology; Gastrointestinal tract; Health aspects; Hepatology; Homeostasis; Homeostasis - immunology; Humans; Immune response; Immunological tolerance; Inflammation; Inflammation - immunology; Inflammation - therapy; Inflammatory bowel diseases; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - therapy; Intestine; Macrophages; Macrophages - immunology; Medicine; Medicine & Public Health; Monocytes; Mucosa; Observations; Remission; Review Article; Therapeutic applications
• ISSN: 1759-5045; 1759-5053
• DOI: 10.1038/s41575-019-0172-4

Macrophages are the gatekeepers of intestinal immune homeostasis as they discriminate between innocuous antigens and potential pathogens to maintain oral tolerance. However, in individuals with a genetic and environmental predisposition, regulation of intestinal immunity is impaired, leading to chronic relapsing immune activation and pathologies of the gastrointestinal tract, such as IBD. As evidence suggests a causal link between defects in the resolution of intestinal inflammation and altered monocyte–macrophage differentiation in patients with IBD, macrophages have been considered as a novel potential target to develop new treatment approaches. This Review discusses the molecular and cellular mechanisms involved in the differentiation and function of intestinal macrophages in homeostasis and inflammation, and their role in resolving the inflammatory process. Understanding the molecular pathways involved in the specification of intestinal macrophages might lead to a new class of targets that promote remission in patients with IBD. Macrophages are the gatekeepers of intestinal immune homeostasis. This Review discusses the molecular and cellular mechanisms involved in the differentiation and function of intestinal macrophages in homeostasis and inflammation, and their role in resolving the inflammatory process. Key points Intestinal macrophages have roles in maintaining tissue homeostasis, in inflammation, and especially in inducing resolution after inflammation. Resolution of inflammation in general is an active process controlled by local recruitment of monocytes and accumulation of alternatively activated macrophages with proresolving capacity. Resolution of intestinal inflammation and mucosal healing is a pivotal step for complete remission of IBD. Findings suggest a causal link between IBD and defects in the transition of monocytes to proresolving macrophages, as exemplified by successful IBD therapies that favour alternatively activated macrophage differentiation. A deeper understanding of the molecular pathways involved in the differentiation and functions of intestinal macrophages might lead to a new class of targets to promote remission in patients with IBD.