title: HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases.
abstract: BACKGROUND
  Various kinds of autoimmune diseases have been reported to have a significant relationship with persistent hepatitis c virus (HCV) infection and Th17 cells. Previously, our group reported that the existence of HCV in T lymphocytes could affect the development of CD4+ helper T cells and their proliferation, in addition to the induction of immunoglobulin hyper-mutation.
  
  
  METHODS
  Therefore, we analyzed the relationship between persistent infection of HCV and the mechanism of Th17 cell induction ex vivo and in vitro.
  
  
  RESULTS
  The prevalence of autoimmune-related diseases in chronic hepatitis c patients (CH-C) was significantly higher than in other types of chronic hepatitis (hepatitis B and NASH). A significantly higher frequency of IL6 and TGF-β double-high patients was detected in CH-C than in other liver diseases. Moreover, these double-high patients had significantly higher positivity of anti-nuclear antibody, cryoglobulinemia, and lymphotropic HCV and higher amounts of IL1-β, IL21, IL23. In addition to the previously reported lymphotropic SB-HCV strain, we found a novel, genotype 1b lymphotropic HCV (Ly-HCV), by deep sequencing analysis. Lymphotropic-HCV replication could be detected in the lymphoid cells with various kinds of cytokine-conditions including IL1β, IL23, IL6 and TGF-β in vitro. Infection by HCV could significantly enhance the development of Th17 cells. The HCV protein responsible for inducing the Th17 cells was HCV-Core protein, which could enhance the STAT-3 signaling and up-regulate the expression of RORγt as a Th17 master gene.
  
  
  CONCLUSIONS
  Infection by lymphotropic HCV might enhance the Th17 development and contribute to understanding the pathogenesis of autoimmune-related diseases.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ninomiya
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.affiliation: Department of Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Keigo
authors.initials: K
authors.lastname: Machida
authors.affiliation: Division of Cell Proliferation, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Funayama
authors.affiliation: Division of Cell Proliferation, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Koju
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kato
authors.affiliation: Division of Cell Proliferation, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America; China Medical University, Taichung, Taiwan.
authors.forename: Michael M C
authors.initials: MM
authors.lastname: Lai
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai City, Miyagi, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D001327:Autoimmune Diseases / Q000209:etiology* / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D003450:Cryoglobulins / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006509:Hepatitis B / Q000150:complications / Q000276:immunology; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology; D006801:Humans; D058504:Th17 Cells / Q000276:immunology* / Q000821:virology
chemical_list: D003450:Cryoglobulins; D016207:Cytokines