Journal
PLOS ONE
Volume 9, Issue 6, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0098521
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Funding
- Ministry of Education, Culture, Sport, Science, and Technology of Japan [21790642, 23790761, 25460970]
- Japan Society of Hepatology
- National Institute on Alcohol Abuse and Alcoholism [R01 AA018857]
- American Cancer Society [RSG-12-177-01]
- Grants-in-Aid for Scientific Research [25460970, 23790761, 26293059, 21790642, 26670085] Funding Source: KAKEN
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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-beta 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-beta, 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 IL1 beta, IL23, IL6 and TGF-beta 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 ROR gamma t as a Th17 master gene. Conclusion: Infection by lymphotropic HCV might enhance the Th17 development and contribute to understanding the pathogenesis of autoimmune-related diseases.
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