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The incidence and prevalence of IBD have been increasing worldwide, but their etiology remains largely unknown. Although anti-TNF agents can be highly effective in IBD patients, 10%\u201340% of patients do not respond to primary anti-TNF therapy. Furthermore, anti-TNF therapy for IBD does not prevent the incidence and progression of fibrosis. A growing body of evidence suggests that IBD pathogenesis is associated with epithelial barrier dysfunction, inappropriate immune responses to luminal microorganisms, and environmental factors as well as host genetics. Recently, a variety of mesenchymal stromal cell populations, including fibroblasts and myofibroblasts, have been characterized in individual tissues under homeostatic and inflammatory conditions. The compositions of fibroblasts and myofibroblasts are altered in the intestinal mucosa of IBD patients, and diverse properties of these cells, such as the production of pro-inflammatory cytokines and extracellular matrix components, are remodeled. Several studies have demonstrated that IBD-specific fibroblasts are involved in anti-TNF therapy refractoriness. Therefore, a better understanding of the interaction among fibroblasts, epithelial cells, immune cells, and microbes associated with the maintenance and perturbation of intestinal homeostasis may facilitate the identification of novel therapeutic targets for IBD. This review presents the key findings obtained to date regarding the pathological and homeostatic mechanisms by which functionally distinct fibroblasts and myofibroblasts regulate epithelial barrier integrity, immunity, and tissue regeneration in health and in gastrointestinal disorders.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf015","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T08:25:19Z","timestamp":1741940719000},"page":"379-392","source":"Crossref","is-referenced-by-count":21,"title":["Roles of fibroblasts in the pathogenesis of inflammatory bowel diseases and IBD-associated fibrosis"],"prefix":"10.1093","volume":"37","author":[{"given":"Takayoshi","family":"Ito","sequence":"first","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University , Suita 565-0871 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