The Role of IL-17 Signaling in Regulation of the Liver–Brain Axis and Intestinal Permeability in Alcoholic Liver Disease

Abstract 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 the 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.
Source: Current Pathobiology Reports - Category: Laboratory Medicine Source Type: research