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

Medientyp: E-Artikel

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

Beteiligte: 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

Quelle: Cells ; 9 ( 2020 ) S. 1949

Erschienen: MDPI AG, 2020

Sprache: Englisch

DOI: 10.3390/cells9091949

ISSN: 2073-4409

Schlagwörter: General Medicine

Zusammenfassung: 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.

Beschreibung: 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.

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