title: Interleukin (IL)-17/IL-22-producing T cells enriched within the liver of patients with chronic hepatitis C viral (HCV) infection.
abstract: BACKGROUND
  Effector CD4+ helper T cells have historically been classified into T helper 1 (Th1) and Th2 based on the production of signature cytokines. The recently identified interleukin (IL)-17 cytokine family plays important roles in host immunity against intracellular pathogens and in chronic inflammatory conditions; data have implicated IL-17 in autoimmune and viral liver disease.
  
  
  METHODS
  This study used three patient groups with HCV infection: acute HCV who either cleared spontaneously or became chronically infected (n = 12), endstage liver disease from whom both peripheral and intrahepatic lymphocytes were studied directly ex vivo (n = 11), and 134 patients with different stages of HCV-related fibrosis from whom serum was collected concurrently with liver biopsy. Normal healthy subjects (n = 41) served as controls.
  
  
  RESULTS
  Acute HCV was not associated with expansion of either CD4+ or CD8+ T cells producing IL-17 (Th17, Tc17) or IL-22, and frequencies did not differ in the blood of patients who cleared versus became persistently infected. The hepatic compartment of chronic HCV patients demonstrated statistically more CD4+ and CD8+ that produced IL-17, IL-22 or both as compared to peripheral blood. These T cells displayed a distinct phenotypic profile, high expression of the homing receptor CD161 and low levels of inhibitory receptors, mucin-domain-containing-molecule-3 (Tim-3) and programmed-death 1. Using a sensitive ELISA, we found no significant differences in serum levels of IL-17 according to HCV-related fibrosis.
  
  
  CONCLUSIONS
  In chronic HCV, T cells producing IL-17/IL-22 may home to the liver; however, circulating levels of IL-17 do not correlate with fibrosis.
authors.affiliation: Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver and National Jewish Hospital, Aurora, CO 80045, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Foster
authors.forename: Lucy
authors.initials: L
authors.lastname: Golden-Mason
authors.forename: Alleluiah
authors.initials: A
authors.lastname: Rutebemberwa
authors.forename: Hugo R
authors.initials: HR
authors.lastname: Rosen
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000097:blood; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D000097043:Interleukin-22