title: Association of colonic regulatory T cells with hepatitis C virus pathogenesis and liver pathology.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, Ohio, USA.|Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Helal F
authors.initials: HF
authors.lastname: Hetta
authors.affiliation: Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Mekky
authors.affiliation: Assiut Liver Institute for Treatment of Hepatitis C, Assiut, Egypt.
authors.forename: Nasr K
authors.initials: NK
authors.lastname: Khalil
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Wegdan A
authors.initials: WA
authors.lastname: Mohamed
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Feky
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Shabaan H
authors.initials: SH
authors.lastname: Ahmed
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Enas A
authors.initials: EA
authors.lastname: Daef
authors.affiliation: Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Mahmoud I
authors.initials: MI
authors.lastname: Nassar
authors.affiliation: Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Medhat
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Mohamed Tarek M
authors.initials: MT
authors.lastname: Shata
mesh_terms: D000328:Adult; D003106:Colon / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008099:Liver / Q000473:pathology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology*; D019562:Viral Load; D055815:Young Adult
chemical_list: D016753:Interleukin-10; D015847:Interleukin-4
keywords: HCV; colonic Treg; cytokines; liver histopathology; viral load.