IL-13 as Target to Reduce Cholestasis and Dysbiosis in Abcb4 Knockout Mice.

The Th2 cytokine IL-13 is involved in biliary epithelial injury and liver fibrosis in patients as well as in animal models. The aim of this study was to investigate IL-13 as a therapeutic target during short term and chronic intrahepatic cholestasis in an Abcb4-knockout mouse model (Abcb4-/-). Lack of IL-13 protected Abcb4-/- mice transiently from cholestasis. This decrease in serum bile acids was accompanied by an enhanced excretion of bile acids and a normalization of fecal bile acid composition. In Abcb4-/-/IL-13-/- double knockout mice, bacterial translocation to the liver was significantly reduced and the intestinal microbiome resembled the commensal composition in wild type animals. In addition, 52-week-old Abcb4-/-IL-13-/- mice showed significantly reduced hepatic fibrosis. Abcb4-/- mice devoid of IL-13 transiently improved cholestasis and converted the composition of the gut microbiota towards healthy conditions. This highlights IL-13 as a potential therapeutic target in biliary diseases.

Citation

Luisa Hahn, Nora Helmrich, Diran Herebian, Ertan Mayatepek, Uta Drebber, Eugen Domann, Stefan Olejniczak, Markus Weigel, Torsten Hain, Timo Rath, Stefan Wirtz, Hans-Joachim Mollenkopf, Nadine Schmidt, Christa Ewers, Anne Baier, Yuri Churin, Anita Windhorst, Ralf Weiskirchen, Ulrich Steinhoff, Elke Roeb, Martin Roderfeld. IL-13 as Target to Reduce Cholestasis and Dysbiosis in Abcb4 Knockout Mice. Cells. 2020 Aug 24;9(9)

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PMID: 32846954

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