PLoS ONE (Jan 2014)

HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases.

  • Yasuteru Kondo,
  • Masashi Ninomiya,
  • Osamu Kimura,
  • Keigo Machida,
  • Ryo Funayama,
  • Takeshi Nagashima,
  • Koju Kobayashi,
  • Eiji Kakazu,
  • Takanobu Kato,
  • Keiko Nakayama,
  • Michael M C Lai,
  • Tooru Shimosegawa

DOI
https://doi.org/10.1371/journal.pone.0098521
Journal volume & issue
Vol. 9, no. 6
p. e98521

Abstract

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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.Therefore, we analyzed the relationship between persistent infection of HCV and the mechanism of Th17 cell induction ex vivo and in vitro.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.Infection by lymphotropic HCV might enhance the Th17 development and contribute to understanding the pathogenesis of autoimmune-related diseases.