dc.date.accessioned | 2024-03-23T17:48:56Z | |
dc.date.available | 2024-03-23T17:48:56Z | |
dc.date.created | 2024-02-14T08:30:38Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Jiang, Xiaojun Otterdal, Kari Chung, Brian K. Maucourant, Christopher Rønneberg, Jørgen Dybevik Zimmer, Christine L Øgaard, Jonas Daniel Sjøberg Boichuk, Yuliia Holm, Sverre Geanon, Daniel Schneditz, Georg Bergquist, Annika Björkström, Niklas K Melum, Espen . Cholangiocytes Modulate Cluster of Differentiation 100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation. Gastroenterology. 2023 | |
dc.identifier.uri | http://hdl.handle.net/10852/110075 | |
dc.description.abstract | Background & Aims
Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms.
Methods
Biopsy specimens of explanted livers and endoscopy-guided sampling were used to assess the CD100 expression by spatial transcriptomics, immune imaging, and high-dimensional flow cytometry. To model pathogenic cholangiocyte-immune cell interaction, splenocytes from mutation-specific mice were cocultured with cholangiocytes. Pathogenic pathways were pinpointed by RNA sequencing analysis of cocultured cells and cross-validated in patient materials.
Results
CD100 is mainly expressed by immune cells in the liver and shows a unique pattern around PSC bile ducts with RNA-level colocalization but poor detection at the protein level. This appears to be due to CD100 cleavage as soluble CD100 is increased. Immunophenotyping suggests biliary-infiltrating T cells as the major source of soluble CD100, which is further supported by reduced surface CD100 on T cells and increased metalloproteinases in cholangiocytes after coculturing. Pathogenic T cells that adhered to cholangiocytes up-regulated genes in the T-helper 17 cell differentiation pathway, and the CD100 mutation boosted this process. Consistently, T-helper 17 cells dominate biliary-resident CD4 T cells in patients.
Conclusions
CD100 exerts its functional impact through cholangiocyte-immune cell cross talk and underscores an active, proinflammatory role of cholangiocytes that can be relevant to novel treatment approaches. | |
dc.language | EN | |
dc.publisher | American Gastroenterology Association Institute | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Cholangiocytes Modulate Cluster of Differentiation 100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation | |
dc.title.alternative | ENEngelskEnglishCholangiocytes Modulate Cluster of Differentiation 100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation | |
dc.type | Journal article | |
dc.creator.author | Jiang, Xiaojun | |
dc.creator.author | Otterdal, Kari | |
dc.creator.author | Chung, Brian K. | |
dc.creator.author | Maucourant, Christopher | |
dc.creator.author | Rønneberg, Jørgen Dybevik | |
dc.creator.author | Zimmer, Christine L | |
dc.creator.author | Øgaard, Jonas Daniel Sjøberg | |
dc.creator.author | Boichuk, Yuliia | |
dc.creator.author | Holm, Sverre | |
dc.creator.author | Geanon, Daniel | |
dc.creator.author | Schneditz, Georg | |
dc.creator.author | Bergquist, Annika | |
dc.creator.author | Björkström, Niklas K | |
dc.creator.author | Melum, Espen | |
cristin.unitcode | 185,53,48,14 | |
cristin.unitname | Institutt for indremedisinsk forskning | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 2245757 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Gastroenterology&rft.volume=&rft.spage=&rft.date=2023 | |
dc.identifier.jtitle | Gastroenterology | |
dc.identifier.pagecount | 13 | |
dc.identifier.doi | https://doi.org/10.1053/j.gastro.2023.11.283 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0016-5085 | |
dc.type.version | PublishedVersion | |