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

TitleInterleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis.
Publication TypeJournal Article
Year of Publication2016
AuthorsGieseck RL, Ramalingam TR, Hart KM, Vannella KM, Cantu DA, Lu W-Y, Ferreira-González S, Forbes SJ, Vallier L, Wynn TA
JournalImmunity
Volume45
Issue1
Pagination145-58
Date Published2016 Jul 19
ISSN1097-4180
Abstract

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. VIDEO ABSTRACT.

DOI10.1016/j.immuni.2016.06.009
Alternate JournalImmunity
PubMed ID27421703
PubMed Central IDPMC4956513
Grant ListZ01 AI000829-11 / / Intramural NIH HHS / United States
Z01 AI001019-01 / / Intramural NIH HHS / United States
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