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

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


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


  • Interleukin-13