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Upon inflammation in inflammatory bowel disease (IBD), they express activation markers, accept trophic signaling by infiltrating neutrophils and macrophages, and are activated by cytokines from helper T cells to produce a narrow spectrum of cytokines and a wider spectrum of chemokines, attract cells of innate and adaptive immunity, orchestrate inflammatory responses, and qualitatively and quantitatively modify the extracellular matrix. Thus, beyond being structural tissue components, they assume active roles in the pathogenesis of complicated IBD. Discrimination between myofibroblasts and fibroblasts may be an oversimplification in light of single-cell sequencing data unveiling the complexity of multiple phenotypes of stromal cells with distinct roles and plasticity. Spatial transcriptomics revealed distinct phenotypes by histologic localization and, more intriguingly, the assembly of mucosal neighborhoods that support spatially distinct functions. Current IBD treatments target inflammation but fail in fibrostenotic or fistulizing disease. Baseline and recent findings on stromal cells, molecules, and pathways involved in disrupted extracellular matrix homeostasis are reviewed to provide relevant pharmacologic targets.<\/jats:p>","DOI":"10.1093\/ibd\/izae066","type":"journal-article","created":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T14:32:09Z","timestamp":1712413929000},"page":"1604-1618","source":"Crossref","is-referenced-by-count":7,"title":["Intestinal Stromal Cells in the Turmoil of Inflammation and Defective Connective Tissue Remodeling in Inflammatory Bowel Disease"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-2040","authenticated-orcid":false,"given":"Ioannis","family":"Drygiannakis","sequence":"first","affiliation":[{"name":"Gastroenterology Research Laboratory, School of Medicine, University of Crete , Heraklion , Greece"},{"name":"Gastroenterology Clinic, University Hospital of Heraklion , Heraklion , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kolios","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace , Alexandroupolis , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Filidou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace , Alexandroupolis , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5492-5717","authenticated-orcid":false,"given":"Giorgos","family":"Bamias","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit, Third Academic Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens , Athens , 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