Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University Medical College, Seoul, South Korea.
Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
Nat Rev Gastroenterol Hepatol. 2019 Sep;16(9):531-543. doi: 10.1038/s41575-019-0172-4. Epub 2019 Jul 16.
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.
巨噬细胞是肠道免疫稳态的守门员，它们能够区分无害抗原和潜在病原体，以维持口服耐受。然而，在具有遗传和环境易感性的个体中，肠道免疫的调节受损，导致胃肠道的慢性复发性免疫激活和病理，如 IBD。有证据表明，肠道炎症消退缺陷与 IBD 患者单核细胞-巨噬细胞分化改变之间存在因果关系，因此巨噬细胞被认为是开发新治疗方法的一个新的潜在靶点。这篇综述讨论了在稳态和炎症中肠道巨噬细胞分化和功能的分子和细胞机制，以及它们在炎症过程中的解决作用。了解参与肠道巨噬细胞特异性的分子途径可能会导致一类新的靶点，促进 IBD 患者的缓解。
