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

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

doi:10.3390/cells9091949

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

Cells. 2020 Aug 24;9(9):1949. doi: 10.3390/cells9091949.

Authors

Luisa Hahn¹, Nora Helmrich¹, Diran Herebian², Ertan Mayatepek², Uta Drebber³, Eugen Domann⁴, Stefan Olejniczak⁴, Markus Weigel⁴, Torsten Hain⁴, Timo Rath⁵, Stefan Wirtz⁵, Hans-Joachim Mollenkopf⁶, Nadine Schmidt⁷, Christa Ewers⁷, Anne Baier¹, Yuri Churin¹, Anita Windhorst⁸, Ralf Weiskirchen⁹, Ulrich Steinhoff¹⁰, Elke Roeb¹, Martin Roderfeld¹

Affiliations

¹ Department of Gastroenterology, Justus-Liebig-University, D-35392 Giessen, Germany.
² Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University, D-40225 Duesseldorf, Germany.
³ Institute for Pathology, University Hospital of Cologne, D-50937 Cologne, Germany.
⁴ Institute of Medical Microbiology, German Centre for Infection Research (DZIF Partner Site Giessen-Marburg-Langen), Justus-Liebig-University, D-35392 Giessen, Germany.
⁵ Department of Medicine 1, Division of Gastroenterology, Pneumology and Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany.
⁶ Core Facility Microarray, Max Planck Institute for Infection Biology, D-10117 Berlin, Germany.
⁷ Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig-University Giessen, D-35392 Giessen, Germany.
⁸ Institute for Medical Informatics, Justus-Liebig-University, D-35392 Giessen, Germany.
⁹ Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital, RWTH Aachen University, D-52074 Aachen, Germany.
¹⁰ Institute for Medical Microbiology and Hospital Hygiene, Philipps University Marburg, D-35043 Marburg, Germany.

Abstract

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.

Keywords: Th2; bacterial translocation; bile acid; intestinal microbiome; liver fibrosis; tight junction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cholestasis, Intrahepatic / therapy*
Disease Models, Animal
Dysbiosis / therapy*
Humans
Interleukin-13 / metabolism*
Mice
Mice, Knockout

Substances

Interleukin-13