Details

Autor(en) / Beteiligte

• Gieseck, Richard L.
• Ramalingam, Thirumalai R.
• Hart, Kevin M.
• Vannella, Kevin M.
• Cantu, David A.
• Lu, Wei-Yu
• Ferreira-González, Sofía
• Forbes, Stuart J.
• Vallier, Ludovic
• Wynn, Thomas A.

Titel

Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis

Ist Teil von

• Immunity (Cambridge, Mass.), 2016-07, Vol.45 (1), p.145-158

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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. [Display omitted] [Display omitted] •Type 2 cell-mediated fibrosis and regeneration are independently regulated by IL-13•Pathological fibrosis is driven by direct IL-13 signaling in PDGFRB+ fibroblasts•IL-13 stimulates hepatobiliary progenitor cells and cholangiocytes to proliferate•IL-13 regulates lipogenesis, bile acid synthesis, and biliary-dependent steatosis Fibroproliferative diseases will affect nearly half of the global population and result in significant loss of quality of life due to comorbidities. In this work, Wynn and colleagues demonstrate that the type 2 cytokine interleukin-13 signals through distinct cellular pathways to simultaneously drive hepatic regeneration, fibrosis, ductular reaction, cholestasis, and steatosis.