| Theme |
Intestinal mucosal immunology update for clinician |
| Title |
Role of intestinal macrophage in the pathogenesis of inflammatory bowel disease |
| Author |
Nobuhiko Kamada |
University of Michigan Medical School / Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine |
| Author |
Toshifumi Hibi |
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine |
| [ Summary ] |
The gut comprises the various kinds of host immune cells as well as commensal microbiota. Unique regulatory immune mechanisms in the gut allow the peaceful co-existance of host immune cells and micobiota. Macrophages promote regulatory immunity and essential for the maintenance of gut homeostasis. Resident macrophages in the mouse intestine produce an anti-inflammatory cytokine IL-10 but not pro-inflammatory cytokines, and promote differentiation and maintenance of regulatory T cells. Intestinal macrophages in the human gut do not produce pro-inflammatory cytokines in response to commensal microbiota, despite they reveal normal phagocytic and bacteriocidal abilities. Once the regulatory function of intestinal macrophages was disrupted, they would respond to the commensal microbiota and result in inflammatory bowel diseases (IBDs). Indeed, intestinal macrophages isolated from inflamed mucosa of IBD patients produce robust pro-inflammatory cytokines, such as IL-23 and TNF-α, in response to microbiota, and these cytokines activate pathogenic Th1, Th17 cells and gut-specific NKp46+ NK cells. Thus, understanding the physiological role of intestinal macrophage will provide new insight into the pathogenesis and development of new therapies for IBDs. |