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

• Published in: Journal of gastroenterology and hepatology Vol. 30; no. 10; pp. 1543 - 1551
• Main Authors: Hetta, Helal F, Mekky, Mohamed A, Khalil, Nasr K, Mohamed, Wegdan A, El-Feky, Mohamed A, Ahmed, Shabaan H, Daef, Enas A, Nassar, Mahmoud I, Medhat, Ahmed, Sherman, Kenneth E, Shata, Mohamed Tarek M
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01-10-2015
• Subjects: Adult; Colon - immunology; Colon - pathology; colonic Treg; cytokines; Female; Fibrosis; HCV; 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; liver histopathology; Lymphocyte Count; Male; Middle Aged; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Viral Load; Young Adult; colonic Treg; HCV; cytokines; viral load; liver histopathology
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/jgh.12936

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.