IL-13 as Target to Reduce Cholestasis and Dysbiosis in <i>Abcb4</i> 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
Affiliations
Luisa Hahn
Department of Gastroenterology, Justus-Liebig-University, D-35392 Giessen, Germany
Nora Helmrich
Department of Gastroenterology, Justus-Liebig-University, D-35392 Giessen, Germany
Diran Herebian
Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University, D-40225 Duesseldorf, Germany
Ertan Mayatepek
Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University, D-40225 Duesseldorf, Germany
Uta Drebber
Institute for Pathology, University Hospital of Cologne, D-50937 Cologne, Germany
Eugen Domann
Institute of Medical Microbiology, German Centre for Infection Research (DZIF Partner Site Giessen-Marburg-Langen), Justus-Liebig-University, D-35392 Giessen, Germany
Stefan Olejniczak
Institute of Medical Microbiology, German Centre for Infection Research (DZIF Partner Site Giessen-Marburg-Langen), Justus-Liebig-University, D-35392 Giessen, Germany
Markus Weigel
Institute of Medical Microbiology, German Centre for Infection Research (DZIF Partner Site Giessen-Marburg-Langen), Justus-Liebig-University, D-35392 Giessen, Germany
Torsten Hain
Institute of Medical Microbiology, German Centre for Infection Research (DZIF Partner Site Giessen-Marburg-Langen), Justus-Liebig-University, D-35392 Giessen, Germany
Timo Rath
Department of Medicine 1, Division of Gastroenterology, Pneumology and Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany
Stefan Wirtz
Department of Medicine 1, Division of Gastroenterology, Pneumology and Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany
Hans-Joachim Mollenkopf
Core Facility Microarray, Max Planck Institute for Infection Biology, D-10117 Berlin, Germany
Nadine Schmidt
Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig-University Giessen, D-35392 Giessen, Germany
Christa Ewers
Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig-University Giessen, D-35392 Giessen, Germany
Anne Baier
Department of Gastroenterology, Justus-Liebig-University, D-35392 Giessen, Germany
Yuri Churin
Department of Gastroenterology, Justus-Liebig-University, D-35392 Giessen, Germany
Anita Windhorst
Institute for Medical Informatics, Justus-Liebig-University, D-35392 Giessen, Germany
Ralf Weiskirchen
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), University Hospital, RWTH Aachen University, D-52074 Aachen, Germany
Ulrich Steinhoff
Institute for Medical Microbiology and Hospital Hygiene, Philipps University Marburg, D-35043 Marburg, Germany
Elke Roeb
Department of Gastroenterology, Justus-Liebig-University, D-35392 Giessen, Germany
Martin Roderfeld
Department of Gastroenterology, Justus-Liebig-University, D-35392 Giessen, Germany
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.
