Interleukin-13 activates distinct cellular pathways leading to ductular reaction, steatosis, and fibrosis

Research output: Contribution to journalArticlepeer-review


  • Richard L. Gieseck III
  • Thirumalai Ramalingam
  • Kevin M. Hart
  • Kevin M. Vannella
  • David A. Cantu
  • Sofia Ferreira-Gonzalez
  • Stuart J. Forbes
  • Ludovic Vallier
  • Thomas A. Wynn

Colleges, School and Institutes

External organisations

  • National Institute of Allergy and Infectious Diseases
  • University of Edinburgh
  • Wellcome Trust-Medical Research Council Stem Cell Institute
  • Wellcome Trust Sanger Institute


Fibroproliferative diseases are driven by dysregulated tissue repair responses and are a major cause of morbidity and mortality because they affect nearly every organ system. Type 2 cytokine responses are critically involved in tissue repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis are not well understood. Here, we have shown that the type 2 effector cytokine interleukin-13 simultaneously, yet independently, directed hepatic fibrosis and the compensatory proliferation of hepatocytes and biliary cells in progressive models of liver disease induced by interleukin-13 overexpression or after infection with Schistosoma mansoni. Using transgenic mice with interleukin-13 signaling genetically disrupted in hepatocytes, cholangiocytes, or resident tissue fibroblasts, we have revealed direct and distinct roles for interleukin-13 in fibrosis, steatosis, cholestasis, and ductular reaction. Together, these studies show that these mechanisms are simultaneously controlled but distinctly regulated by interleukin-13 signaling. Thus, it may be possible to promote interleukin-13-dependent hepatobiliary expansion without generating pathological fibrosis.


Original languageEnglish
Pages (from-to)145-158
Number of pages14
Issue number1
Early online date12 Jul 2016
Publication statusPublished - 19 Jul 2016