CD47: an immunoregulatory nexus in liver and gastrointestinal disorders

Abstract Cluster of differentiation 47 (CD47) is a widely expressed transmembrane protein that serves as a critical immunoregulatory checkpoint in both homeostatic and pathological conditions of the digestive system. It interacts with signal regulatory protein alpha to send a ‘do not eat me’ signal, thereby preventing phagocytosis and shaping immune responses. Beyond immunity, CD47 also influences cell death, growth and metabolism through interactions with integrins and thrombospondin-1. Recent studies implicate CD47 as a central nexus in the pathogenesis of diverse liver and gastrointestinal disorders, including metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, inflammatory bowel disease, liver ischaemia-reperfusion injury, drug-induced liver injury and gastrointestinal malignancies such as hepatocellular carcinoma, colorectal and pancreatic cancers. CD47 contributes to disease progression through immune modulation, endothelial dysfunction, fibrogenic activation and suppression of antitumour immunity. This review summarises current mechanistic insights into CD47 signalling across digestive diseases and highlights its emerging potential as a therapeutic target for immunometabolic and oncological interventions in gastroenterology and hepatology.