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Although barrier dysfunction and immune activation are implicated, underlying mechanisms remain unclear. The aim of this study was to characterize enteric glial cells (EGC) and mast cell distribution across MC subtypes, assess treatment effects, and explore EGC-related gene expression and barrier markers. Colonic biopsies from patients with active collagenous colitis (aCC), budesonide-refractory CC (rCC), and active lymphocytic colitis (LC) were compared to irritable bowel syndrome (IBS), ulcerative colitis (UC), and healthy controls (HC). A subset of CC patients was studied during active disease (aCC) and in clinical remission due to budesonide treatment (tCC). Immunofluorescence quantified EGC positive for glial fibrillary acidic protein (EGCGFAP+) and S100 calcium-binding protein B (EGCS100\u03b2+), mast cell tryptase, and tight junction proteins. RNA-sequencing assessed EGC-related gene expression. Results showed that EGCGFAP+ were highest in rCC and decreased following budesonide treatment in aCC, whereas EGCS100\u03b2+ were highest in aCC, remained unchanged following treatment, resembled IBS, and were reduced compared with UC. Mast cell numbers were higher in aCC than in HC and rCC but remained unchanged following treatment, while mast cell degranulation decreased after treatment. Tight junction proteins were unchanged. RNA-sequencing indicated differential regulation of EGC-related genes. In conclusion, MC shows subtype-specific alterations involving EGC and mast cells, suggesting distinct glial states and differential treatment responsiveness. Our findings support the presence of distinct neuroimmune alterations in CC and LC and highlight EGC as potential contributors to MC pathophysiology.<\/jats:p>","DOI":"10.3390\/cells15191778","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:33:12Z","timestamp":1790699592000},"page":"1778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Enteric Glial and Mast Cell Characteristics Distinguish Microscopic Colitis Subtypes Relative to Healthy and Disease Controls, with Treatment-Associated Reductions in Glial Reactivity and Mast Cell Degranulation in Collagenous Colitis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3952-5926","authenticated-orcid":false,"given":"Julie","family":"Beaudeau","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 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