Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease

Y. Tang, Z. Bian, L. Zhao, Y. Liu, S. Liang, Q. Wang, X. Han, Y. Peng, X. Chen, L. Shen, D. Qiu, Zhiping Li, X. Ma

Research output: Contribution to journalArticle

Abstract

Mechanisms associated with the progression of simple steatosis to non-alcoholic fatty liver disease (NAFLD) remain undefined. Regulatory T cells (T regs) play a critical role in regulating inflammatory processes in non-alcoholic steatohepatitis (NASH) and because T helper type 17 (Th17) functionally oppose T reg-mediated responses, this study focused on characterizing the role of Th17 cells using a NAFLD mouse model. C57BL/6 mice were fed either a normal diet (ND) or high fat (HF) diet for 8 weeks. Mice in the HF group had a significantly higher frequency of liver Th17 cells compared to ND-fed mice. Neutralization of interleukin (IL)-17 in HF mice ameliorated lipopolysaccharide (LPS)-induced liver injury reflected by decreased serum alanine aminotransferase (ALT) levels and reduced inflammatory cell infiltrates in the liver. In vitro, HepG2 cells cultured in the presence of free fatty acids (FFA; oleic acid and palmitic acid) for 24 h and IL-17 developed steatosis via insulin-signalling pathway interference. IL-17 and FFAs synergized to induce IL-6 production by HepG2 cells and murine primary hepatocytes which, in combination with transforming growth factor (TGF-β), expanded Th17 cells. It is likely that a similar process occurs in NASH patients, as there were significant levels of IL-17 + cell infiltrates in NASH patient livers. The hepatic expression of Th17 cell-related genes [retinoid-related orphan receptor gamma (ROR)γt, IL-17, IL-21 and IL-23] was also increased significantly in NASH patients compared to healthy controls. Th17 cells and IL-17 were associated with hepatic steatosis and proinflammatory response in NAFLD and facilitated the transition from simple steatosis to steatohepatitis. Strategies designed to alter the balance between Th17 cells and T regs should be explored as a means of preventing progression to NASH and advanced liver diseases in NAFLD patients.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalClinical and Experimental Immunology
Volume166
Issue number2
DOIs
StatePublished - Nov 2011

Fingerprint

Th17 Cells
Interleukin-17
Fatty Liver
Inflammation
Liver
Hep G2 Cells
Fats
Diet
Interleukin-23
Palmitic Acid
Retinoids
Transforming Growth Factors
High Fat Diet
Regulatory T-Lymphocytes
Oleic Acid
Alanine Transaminase
Inbred C57BL Mouse
Nonesterified Fatty Acids
Lipopolysaccharides
Non-alcoholic Fatty Liver Disease

Keywords

  • Inflammation
  • Insulin resistance
  • Non-alcoholic steatohepatitis
  • Signalling pathways
  • Th17 cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease. / Tang, Y.; Bian, Z.; Zhao, L.; Liu, Y.; Liang, S.; Wang, Q.; Han, X.; Peng, Y.; Chen, X.; Shen, L.; Qiu, D.; Li, Zhiping; Ma, X.

In: Clinical and Experimental Immunology, Vol. 166, No. 2, 11.2011, p. 281-290.

Research output: Contribution to journalArticle

Tang, Y, Bian, Z, Zhao, L, Liu, Y, Liang, S, Wang, Q, Han, X, Peng, Y, Chen, X, Shen, L, Qiu, D, Li, Z & Ma, X 2011, 'Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease', Clinical and Experimental Immunology, vol. 166, no. 2, pp. 281-290. https://doi.org/10.1111/j.1365-2249.2011.04471.x
Tang, Y. ; Bian, Z. ; Zhao, L. ; Liu, Y. ; Liang, S. ; Wang, Q. ; Han, X. ; Peng, Y. ; Chen, X. ; Shen, L. ; Qiu, D. ; Li, Zhiping ; Ma, X. / Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease. In: Clinical and Experimental Immunology. 2011 ; Vol. 166, No. 2. pp. 281-290.
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