Comprehensive analysis of immune response in hapatitis B using novel disease mouse model

• Project/Area Number: 25460991
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: Takahashi Ken 京都大学, 医学(系)研究科(研究院), 助教 (60594372)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ウイルス肝炎 / 免疫学 / 肝臓病学 / 肝炎ウイルス

Outline of Final Research Achievements

Deeper understanding of the immunopathogenesis of hepatitis B is needed to develop an effective therapy for terminating HBV infection. The aim of this study was to gain comprehensive insight into the immune response to HBV at the transcriptional level. Highly sensitive transcriptome analysis of newly developed HBV model mouse in which HBs antigen is expressed in a liver-specific and time-controlled manner showed that immunological status of inflamed liver was Th1-biased but concomitantly immunosuppressive. The unexpected upregulation of co-inhibitory genes observed in our model implies that adaptive immunity against HBV is regulated by the balance between stimulatory and inhibitory forces as early as the acute phase of infection. In another series of experiments, transcriptome analysis of HBV-infected cells was also performed. The results showed that HBV does not induce a measurable innate immune response in the hepatocytes.

Research Products

• [Journal Article] Human plasmacytoid dendritic cells sense lymphocytic choriomeningitis virus-infected cells in vitro (2014)
  • Author(s): Wieland SF, Takahashi K, Boyd B, Whitten-Bauer C, Ngo N, de la Torre JC, Chisari FV.
  • Journal Title: Journal of Virology Volume: 88 Issue: 1 Pages: 752-757
  • DOI: 10.1128/jvi.01714-13
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mouse models of hepatitis B virus infection comprising host-virus immunologic interactions (2014)
  • Author(s): Inuzuka T, Takahashi K, Chiba T, Marusawa H.
  • Journal Title: Pathogens Volume: 3 Issue: 2 Pages: 377-389
  • DOI: 10.3390/pathogens3020377
  • Peer Reviewed / Open Access
• [Presentation] RNA-seq analysis of innate immune response in hepatitis B (2016)
  • Author(s): Ken Takahashi
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: SanDiego, CA, USA
  • Year and Date: 2016-05-24
  • Int'l Joint Research
• [Presentation] B型肝炎の免疫応答解析におけるRNA-seqの有用性 (2015)
  • Author(s): 高橋健
  • Organizer: 第41回日本肝臓学会西部会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-12-04