Association of colonic regulatory T cells with hepatitis C virus pathogenesis and liver pathology

J Gastroenterol Hepatol. 2015 Oct;30(10):1543-51. doi: 10.1111/jgh.12936.

Abstract

Background and aim: Forkhead box protein P3 (FoxP3)(+) regulatory T (Treg ) cells play a fundamental role in maintaining the balance between the tissue-damaging and protective immune response to chronic hepatitis C (CHC) infection. Herein, we investigated the frequency of Treg cells in the colon and their potential relationship to the various CHC outcomes and hepatic histopathology.

Methods: Colonic biopsies were collected from three groups with CHC: treatment naïve (TN; n = 20), non-responders (NR; n = 20), sustained virologic response (SVR; n = 20), and a fourth healthy control group (n = 10). The plasma viral loads and cytokines levels were determined by quantitative real-time polymerase chain reaction, and ELISA, respectively. Liver biopsies were examined to assess inflammatory score and fibrosis stage. Colonic Treg frequency was estimated by immunohistochemistry using confocal microscopy.

Results: A significant increase in the frequency of colonic Treg was found in TN, and NR groups compared with the control and SVR group. The frequency of colonic Treg , plasma interleukin (IL)-10 and IL-4 levels were significantly positively correlated with viral load and negatively correlated with METAVIR inflammatory score, and fibrosis stages.

Conclusion: Colonic Treg cells are negatively correlated with liver inflammation and hepatitis C virus (HCV) viral load, which suggests a strong linkage between gut-derived Treg cell populations and HCV infection.

Keywords: HCV; colonic Treg; cytokines; liver histopathology; viral load..

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colon / immunology*
  • Colon / pathology*
  • Female
  • Fibrosis
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / pathology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interleukin-10 / blood
  • Interleukin-4 / blood
  • Liver / pathology*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology*
  • Viral Load
  • Young Adult

Substances

  • Interleukin-10
  • Interleukin-4