The analysis of IFN-lambda related innate immunity and the mechanism of immne escape of HBV using human induced pluripotent stem cell-derived hepatic cell lines.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15931
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MURAKAWA Miyako 東京医科歯科大学, 医学部附属病院, 助教 (20733851)
• Research Collaborator: ASANIHA Yasuhiro ; KAKINUMA Sei
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: インターフェロンラムダ / ウイルス性肝炎 / 発癌

Outline of Final Research Achievements

We investigated the role of IFN-λ on chronic viral hepatitis using both human induced pluripotent stem cell-derived hepatic cell lines and liver biopsy samples, blood samples, and clinical data obtained from the patients with viral hepatitis. The difference of anti-viral effect and expression of ISGs according to the expression levels of IFNL were shown in our study. Moreover, we found that the risk for HCC development were high in the patients under the antiviral treatment with higher expression levels of serum IFN-λ3. Additionally, by the sub-analysis of HBV clinical data, we confirmed the relationship between diabetes mellitus and HCC development in the patients in whom HBV replication were suppressed well.

Free Research Field

ウイルス肝炎

Academic Significance and Societal Importance of the Research Achievements

今回、新規抗HBV治療薬の開発に直結する成果は得られなかったが、IFNλの機能には未だ不明点が多い中で、ウイルスが駆除された状況でもIFNλ3が誘導され、かつその後の発癌とも関連するという新たな知見は、今後問題となり続ける抗ウイルス治療後発癌に対する治療戦略における新たなターゲットを見出せた点で有意義である。また、IFNλ3の抗HBV作用について臨床データを用いた再検証を行う中で、現在急増している糖尿病がHBV肝癌に関わることを示したことは、癌健診の啓蒙などの社会的意義も大きい。