Cells · 2020
IL-13 as Target to Reduce Cholestasis and Dysbiosis in Abcb4 Knockout Mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Hahn Luisa, Helmrich Nora, Herebian Diran, Mayatepek Ertan, Drebber Uta, Domann Eugen, Olejniczak Stefan, Weigel Markus, Hain Torsten, Rath Timo, Wirtz Stefan, Mollenkopf Hans-Joachim, Schmidt Nadine, Ewers Christa, Baier Anne, Churin Yuri, Windhorst Anita, Weiskirchen Ralf, Steinhoff Ulrich, Roeb Elke, Roderfeld Martin
Аннотация
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.