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Semin Liver Dis 2021; 41(04): 507-515
DOI: 10.1055/s-0041-1730926
Review Article

Interleukin-17 in Liver Disease Pathogenesis

Na Li
1   Shanghai University of Medicine & Health Sciences, Shanghai, P.R. China
2   Department of Medicine, University of California, San Diego, La Jolla, CA
3   Department of Surgery, University of California, San Diego, La Jolla, CA
,
Gen Yamamoto
2   Department of Medicine, University of California, San Diego, La Jolla, CA
3   Department of Surgery, University of California, San Diego, La Jolla, CA
,
Hiroaki Fuji
2   Department of Medicine, University of California, San Diego, La Jolla, CA
3   Department of Surgery, University of California, San Diego, La Jolla, CA
,
Tatiana Kisseleva
3   Department of Surgery, University of California, San Diego, La Jolla, CA
› Author Affiliations Funding This study was supported by the National Institutes of Health, grant nos.: R01 DK101737–01A1, U01 AA022614–01A1, R01 DK099205–01A1, and P50AA011999.
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Abstract

Interleukin 17A (IL-17A)-producing T helper 17 (Th17) cells were identified as a subset of T helper cells that play a critical role in host defense against bacterial and fungal pathogens. Th17 cells differentiate from Th0 naïve T-cells in response to transforming growth factor β1 (TGF-β1) and IL-6, the cytokines which also drive development of liver fibrosis, require activation of transcription factor retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt). IL-17A signals through the ubiquitously expressed receptor IL-17RA. Expression of IL-17RA is upregulated in patients with hepatitis B virus/hepatitis C virus (HBV/HCV) infections, nonalcoholic steatohepatitis (NASH), alcohol-associated liver disease (AALD), hepatocellular carcinoma (HCC), and experimental models of chronic toxic liver injury. The role of IL-17 signaling in the pathogenesis of NASH- and AALD-induced metabolic liver injury and HCC will be the focus of this review. The role of IL-17A–IL-17RA axis in mediation of the cross-talk between metabolically injured hepatic macrophages, hepatocytes, and fibrogenic myofibroblasts will be discussed.

Keywords

IL-17 signaling - metabolic syndrome - lipogenesis - TNF signaling


Publication History

Article published online:
15 June 2021

© 2021. Thieme. All rights reserved.

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