A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis

TY - JOUR

T1 - A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis

AU - Stumme, Friederike

AU - Steffens, Niklas

AU - Steglich, Babett

AU - Mathies, Franziska

AU - Nawrocki, Mikolaj

AU - Sabihi, Morsal

AU - Soukou-Wargalla, Shiwa

AU - Göke, Emilia

AU - Kempski, Jan

AU - Fründt, Thorben

AU - Weidemann, Sören

AU - Schramm, Christoph

AU - Gagliani, Nicola

AU - Huber, Samuel

AU - Bedke, Tanja

N1 - Copyright © 2024 Stumme, Steffens, Steglich, Mathies, Nawrocki, Sabihi, Soukou-Wargalla, Göke, Kempski, Fründt, Weidemann, Schramm, Gagliani, Huber and Bedke.

PY - 2024/3/6

Y1 - 2024/3/6

N2 - BACKGROUND: Primary 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.METHODS: Mdr2-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.RESULTS: Using 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.CONCLUSIONS: We 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.

AB - BACKGROUND: Primary 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.METHODS: Mdr2-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.RESULTS: Using 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.CONCLUSIONS: We 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.

KW - Humans

KW - Animals

KW - Mice

KW - Cholangitis, Sclerosing/drug therapy

KW - Inflammatory Bowel Diseases/pathology

KW - Inflammation

KW - Colitis

KW - Liver Cirrhosis/pathology

U2 - 10.3389/fimmu.2024.1307297

DO - 10.3389/fimmu.2024.1307297

M3 - SCORING: Journal article

C2 - 38510236

VL - 15

SP - 1307297

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -