A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis
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A protective effect of inflammatory bowel disease on the severity of sclerosing cholangitis. / Stumme, Friederike; Steffens, Niklas; Steglich, Babett; Mathies, Franziska; Nawrocki, Mikolaj; Sabihi, Morsal; Soukou-Wargalla, Shiwa; Göke, Emilia; Kempski, Jan; Fründt, Thorben; Weidemann, Sören; Schramm, Christoph; Gagliani, Nicola; Huber, Samuel; Bedke, Tanja.
In: FRONT IMMUNOL, Vol. 15, 06.03.2024, p. 1307297.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -