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Previous studies have identified impairments in both systemic and local iron metabolism in IBD patients. However, the impact of iron dyshomeostasis on the development and pathogenesis of IBD remains elusive. In this study, we confirmed iron deposition in inflamed intestinal lesions of IBD patients and mice with DSS\u2010induced colitis, accompanied by distinct distribution patterns of the iron storage protein ferritin. To reveal the role of ferritin in the involvement of pathology of IBD, we constructed intestinal epithelial cell\u2010 or myeloid\u2010specific ferritin H (<jats:italic>FtH<\/jats:italic>) knockout mice and demonstrated that intestinal epithelial cells (IECs) release extracellular vesicles (EVs) that contain iron\u2010loaded ferritin. These EVs are internalized by macrophages via the macrophage scavenger receptor 1 (Msr1), leading to the activation of inflammatory responses and oxidative stress, thereby exacerbating colitis severity. Genetic deletion of <jats:italic>FtH<\/jats:italic> in IECs or blockage of macrophage ferritin uptake, either through Msr1 inhibitor fucoidan or through <jats:italic>Msr1<\/jats:italic> knockdown (KD), suppressed inflammatory symptoms. Thus, EVs containing iron\u2010loaded ferritin released from IECs activate macrophages and contribute to IBD development, supporting that IBD patients with iron deficiency anaemia are often prescribed iron supplementation in a remission phase, other than in an active phase of the disease. Pharmacological inhibition of this ferritin secretion and engulfing process provides a therapeutic target for the disease.<\/jats:p>","DOI":"10.1002\/jev2.70105","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T03:53:46Z","timestamp":1750650826000},"source":"Crossref","is-referenced-by-count":13,"title":["Macrophages Internalize Epithelial\u2010Derived Extracellular Vesicles That Contain Ferritin via the Macrophage Scavenger Receptor 1 to Promote Inflammatory Bowel Disease"],"prefix":"10.1002","volume":"14","author":[{"given":"Wenxin","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Jiangsu Key Laboratory of Molecular Medicine, Medical School Nanjing University  Nanjing 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