Analysis of immune response mechanisms of CTL and NK cells in HBV infection HBV infection

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hiroshima University
• Principal Investigator: Tsuge Masataka 広島大学, 医系科学研究科(医), 准教授 (50448263)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: B型肝炎ウイルス / 免疫寛容 / ヒト肝細胞キメラマウス / 遺伝子発現解析 / 次世代シークエンス解析

Outline of Final Research Achievements

It has not been fully clarified the host immune responses in HBV carriers. I conducted the present study to clarify the mechanism of recognizing HBV infection by host immune cells. First, I compared gene expression profiles between HBV-infected and uninfected humanized mouse livers, and I identified TRAIL-R3 as one of the genes which were significantly regulated by HBV infection. To clarify the association between HBV infection and TRAIL-R3 uprgulation, the reporter assay was performed and I found that the transcriptional activation of TRAIL-R3 was induced by HBx via NF-kB signailing. Additionaly, I also demonstrated that upregulation of TRAIL-R3 could induce the resistance to TRAIL-dependent apoptosis. These results indicated that HBV might induce TRAIL-R3 expression to escape host immune responses for maintaining chronic infection.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

B型肝炎ウイルスは感染後、宿主の免疫寛容状態を誘導し、ヒト肝細胞に持続感染するがそのメカニズムは不明である。本研究成果により、B型肝炎ウイルス感染によって細胞内のTRAIL-R3発現が亢進し、B型肝炎ウイルス感染肝細胞におけるTRAIL誘導性アポトーシスの回避、B型肝炎ウイルス増殖の活性化が誘導され、B型肝炎ウイルスの宿主免疫回避、感染維持に寄与することが明らかとなった。この回避機構を制御することにより、宿主のB型肝炎ウイルスに対する免疫応答を回復させることが可能であり、ヒト肝細胞からのB型肝炎ウイルス完全排除に向けた治療標的となる可能性がある。