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- Bhardwaj, ArchanaUniv Kiel, Germany; Univ Hosp Schleswig Holstein, Germany (author)
Lymphocytic colitis can be transcriptionally divided into channelopathic and inflammatory lymphocytic colitis
- Article/chapterEnglish2024
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- 2024
- JOHN WILEY & SONS LTD,2024
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- LIBRIS-ID:oai:DiVA.org:liu-201312
- https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-201312URI
- https://doi.org/10.1002/ueg2.12531DOI
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- Language:English
- Summary in:English
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- Funding Agencies|Knut och Alice Wallenbergs Stiftelse; Deutsche Forschungsgemeinschaft; Ferring; Region Ostergotland
- BackgroundThe pathobiology of the non-destructive inflammatory bowel disease (IBD) lymphocytic colitis (LC) is poorly understood. We aimed to define an LC-specific mucosal transcriptome to gain insight into LC pathology, identify unique genomic signatures, and uncover potentially druggable disease pathways.MethodsWe performed bulk RNA-sequencing of LC and collagenous colitis (CC) colonic mucosa from patients with active disease, and healthy controls (n = 4-10 per cohort). Differential gene expression was analyzed by gene-set enrichment and deconvolution analyses to identify pathologically relevant pathways and cells, respectively, altered in LC. Key findings were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared our data with a previous cohort of ulcerative colitis and Crohn's disease patients (n = 4 per group) to distinguish non-destructive from classic IBD.ResultsLC can be subdivided into channelopathic LC, which is governed by organic acid and ion transport dysregulation, and inflammatory LC, which is driven by microbial immune responses. Inflammatory LC displays an innate and adaptive immunity that is limited compared to CC and classic IBD. Conversely, we noted a distinct induction of regulatory non-coding RNA species in inflammatory LC samples. Moreover, compared with CC, water channel and cell adhesion molecule gene expression decreased in channelopathic LC, whereas it was accentuated in inflammatory LC and associated with reduced intestinal epithelial cell proliferation.ConclusionsWe conclude that LC can be subdivided into channelopathic LC and inflammatory LC that could be pathomechanistically distinct subtypes despite their shared clinical presentation. Inflammatory LC exhibits a dampened immune response compared to CC and classic IBDs. Our results point to regulatory micro-RNAs as a potential disease-specific feature that may be amenable to therapeutic intervention. image
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Gastroenterologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Gastroenterology and Hepatology hsv//eng
- channelopathic lymphocytic colitis; lymphocytic colitis; microscopic colitis; RNA sequencing
Added entries (persons, corporate bodies, meetings, titles ...)
- Münch, AndreasLinköpings universitet,Avdelningen för molekylär medicin och virologi,Institutionen för hälsa, medicin och vård,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken(Swepub:liu)andsa76 (author)
- Montague, JuliaUniv Kiel, Germany; Univ Hosp Schleswig Holstein, Germany (author)
- Koch, StefanLinköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Wallenberg Centre for Molecular Medicine (WCMM)(Swepub:liu)steko54 (author)
- Rosenstiel, PhilipUniv Kiel, Germany; Univ Hosp Schleswig Holstein, Germany (author)
- Escudero-Hernández, CeliaLinköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Univ Kiel, Germany; Univ Hosp Schleswig Holstein, Germany(Swepub:liu)celes93 (author)
- Univ Kiel, Germany; Univ Hosp Schleswig Holstein, GermanyAvdelningen för molekylär medicin och virologi (creator_code:org_t)
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- In:United European Gastroenterology journal: JOHN WILEY & SONS LTD2050-64062050-6414
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