Inhibition of SATB1 expression in regulatory T cells contributes to hepatitis B virus-related chronic liver inflammation

Mol Med Rep. 2015 Jan;11(1):231-6. doi: 10.3892/mmr.2014.2752. Epub 2014 Oct 23.

Abstract

Regulatory T cells (Tregs) contribute to the pathogenesis of chronic hepatitis B (CHB). Special AT-rich sequence-binding protein 1 (SATB1) may be a key component of this process. In the present study, Tregs and conventional T cells (Tconvs) were isolated by magnetic cell sorting of peripheral blood from CHB patients (n=57), individuals with resolved hepatitis B virus (HBV) infections (n=15), and healthy controls (n=29). SATB1 expression was studied by reverse transcription-quantitative PCR, flow cytometry and immunofluorescence microscopy, and the correlation of SATB1 expression to the expression of liver inflammation serum markers and the HBV DNA load was assessed. CHB patients showed significantly reduced SATB1 expression in Tregs than healthy controls and individuals with resolved HBV infections. Moreover, SATB1 expression in Tregs was significantly lower than in Tconvs of patients with chronic HBV infection. Serum HBV DNA and liver inflammation markers were inversely correlated to the SATB1 mRNA level in Tregs. Antiviral treatment was accompanied by increased expression of the SATB1 gene in Tregs. Thus, Tregs from CHB patients have reduced levels of SATB1, which is resolved with antiviral therapy. Inhibition of SATB1 expression may impair the hepatic inflammatory response and contribute to HBV persistence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation / drug effects
  • Gene Expression*
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / immunology
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Immunophenotyping
  • Interferon alpha-2
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use
  • Liver Function Tests
  • Male
  • Matrix Attachment Region Binding Proteins / genetics*
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use
  • RNA, Messenger / genetics
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Matrix Attachment Region Binding Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • SATB1 protein, human
  • Polyethylene Glycols
  • peginterferon alfa-2b