A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis
BackgroundPrimary sclerosing cholangitis (PSC) is a chronic liver disease marked by inflammation of the bile ducts and results in the development of strictures and fibrosis. A robust clinical correlation exists between PSC and inflammatory bowel disease (IBD). At present, published data are controve...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1307297/full |
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| author | Friederike Stumme Friederike Stumme Niklas Steffens Babett Steglich Babett Steglich Babett Steglich Franziska Mathies Mikolaj Nawrocki Mikolaj Nawrocki Morsal Sabihi Morsal Sabihi Shiwa Soukou-Wargalla Emilia Göke Emilia Göke Jan Kempski Jan Kempski Thorben Fründt Sören Weidemann Christoph Schramm Christoph Schramm Christoph Schramm Nicola Gagliani Nicola Gagliani Nicola Gagliani Samuel Huber Samuel Huber Tanja Bedke Tanja Bedke |
| author_facet | Friederike Stumme Friederike Stumme Niklas Steffens Babett Steglich Babett Steglich Babett Steglich Franziska Mathies Mikolaj Nawrocki Mikolaj Nawrocki Morsal Sabihi Morsal Sabihi Shiwa Soukou-Wargalla Emilia Göke Emilia Göke Jan Kempski Jan Kempski Thorben Fründt Sören Weidemann Christoph Schramm Christoph Schramm Christoph Schramm Nicola Gagliani Nicola Gagliani Nicola Gagliani Samuel Huber Samuel Huber Tanja Bedke Tanja Bedke |
| author_sort | Friederike Stumme |
| collection | DOAJ |
| description | BackgroundPrimary sclerosing cholangitis (PSC) is a chronic liver disease marked by inflammation of the bile ducts and results in the development of strictures and fibrosis. A robust clinical correlation exists between PSC and inflammatory bowel disease (IBD). At present, published data are controversial, and it is yet unclear whether IBD drives or attenuates PSC.MethodsMdr2-deficient mice or DDC-fed mice were used as experimental models for sclerosing cholangitis. Additionally, colitis was induced in mice with experimental sclerosing cholangitis, either through infection with Citrobacter rodentium or by feeding with DSS. Lastly, fibrosis levels were determined through FibroScan analysis in people with PSC and PSC-IBD.ResultsUsing two distinct experimental models of colitis and two models of sclerosing cholangitis, we found that colitis does not aggravate liver pathology, but rather reduces liver inflammation and liver fibrosis. Likewise, people with PSC-IBD have decreased liver fibrosis compared to those with PSC alone.ConclusionsWe found evidence that intestinal inflammation attenuates liver pathology. This study serves as a basis for further research on the pathogenesis of PSC and PSC-IBD, as well as the molecular mechanism responsible for the protective effect of IBD on PSC development. This study could lead to the discovery of novel therapeutic targets for PSC. |
| first_indexed | 2024-03-07T14:31:36Z |
| format | Article |
| id | doaj.art-fe4be545b6ce4708b789790c53a8eb4c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T14:31:36Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fe4be545b6ce4708b789790c53a8eb4c2024-03-06T04:39:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13072971307297A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitisFriederike Stumme0Friederike Stumme1Niklas Steffens2Babett Steglich3Babett Steglich4Babett Steglich5Franziska Mathies6Mikolaj Nawrocki7Mikolaj Nawrocki8Morsal Sabihi9Morsal Sabihi10Shiwa Soukou-Wargalla11Emilia Göke12Emilia Göke13Jan Kempski14Jan Kempski15Thorben Fründt16Sören Weidemann17Christoph Schramm18Christoph Schramm19Christoph Schramm20Nicola Gagliani21Nicola Gagliani22Nicola Gagliani23Samuel Huber24Samuel Huber25Tanja Bedke26Tanja Bedke27Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyCenter of Diagnostics, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMartin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyBackgroundPrimary sclerosing cholangitis (PSC) is a chronic liver disease marked by inflammation of the bile ducts and results in the development of strictures and fibrosis. A robust clinical correlation exists between PSC and inflammatory bowel disease (IBD). At present, published data are controversial, and it is yet unclear whether IBD drives or attenuates PSC.MethodsMdr2-deficient mice or DDC-fed mice were used as experimental models for sclerosing cholangitis. Additionally, colitis was induced in mice with experimental sclerosing cholangitis, either through infection with Citrobacter rodentium or by feeding with DSS. Lastly, fibrosis levels were determined through FibroScan analysis in people with PSC and PSC-IBD.ResultsUsing two distinct experimental models of colitis and two models of sclerosing cholangitis, we found that colitis does not aggravate liver pathology, but rather reduces liver inflammation and liver fibrosis. Likewise, people with PSC-IBD have decreased liver fibrosis compared to those with PSC alone.ConclusionsWe found evidence that intestinal inflammation attenuates liver pathology. This study serves as a basis for further research on the pathogenesis of PSC and PSC-IBD, as well as the molecular mechanism responsible for the protective effect of IBD on PSC development. This study could lead to the discovery of novel therapeutic targets for PSC.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1307297/fullprimary sclerosing cholangitisinflammatory bowel diseaseMdr2 knock outmicrobiotacolitis |
| spellingShingle | Friederike Stumme Friederike Stumme Niklas Steffens Babett Steglich Babett Steglich Babett Steglich Franziska Mathies Mikolaj Nawrocki Mikolaj Nawrocki Morsal Sabihi Morsal Sabihi Shiwa Soukou-Wargalla Emilia Göke Emilia Göke Jan Kempski Jan Kempski Thorben Fründt Sören Weidemann Christoph Schramm Christoph Schramm Christoph Schramm Nicola Gagliani Nicola Gagliani Nicola Gagliani Samuel Huber Samuel Huber Tanja Bedke Tanja Bedke A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis Frontiers in Immunology primary sclerosing cholangitis inflammatory bowel disease Mdr2 knock out microbiota colitis |
| title | A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis |
| title_full | A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis |
| title_fullStr | A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis |
| title_full_unstemmed | A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis |
| title_short | A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis |
| title_sort | protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis |
| topic | primary sclerosing cholangitis inflammatory bowel disease Mdr2 knock out microbiota colitis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1307297/full |
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