The role of IL-17 signaling in regulation of the liver-brain axis and intestinal permeability in Alcoholic Liver Disease

Curr Pathobiol Rep. 2016 Mar;4(1):27-35. doi: 10.1007/s40139-016-0097-3. Epub 2016 Feb 19.


Alcoholic liver disease (ALD) progresses from a normal liver, to steatosis, steatohepatitis, fibrosis and hepatocellular carcinoma (HCC). Despite intensive studies, the pathogenesis of ALD is poorly understood, in part due to a lack of suitable animal models which mimic the stages of ALD progression. Furthermore, the role of IL-17 in ALD has not been evaluated. We and others have recently demonstrated that IL-17 signaling plays a critical role in development of liver fibrosis and cancer. Here we summarize the most recent evidence supporting the role of IL-17 in ALD. As a result of a collaborative effort of Drs. Karin, Gao, Tsukamoto and Kisseleva, we developed several improved models of ALD in mice: 1) chronic-plus-binge model that mimics early stages of steatohepatitis, 2) intragastric ethanol feeding model that mimics alcoholic steatohepatitis and fibrosis, and 3) diethylnitrosamine (DEN)+alcohol model that mimics alcoholic liver cancer. These models might provide new insights into the mechanism of IL-17 signaling in ALD and help identify novel therapeutic targets.

Keywords: Adaptive Immunity; Cytokines; Inflammation; Innate Immunity; activated myofibroblasts; alcoholic liver disease; ethanol metabolism; hepatocellular carcinoma; regression of liver fibrosis.