Elucidation of the onset mechanism of Type 2 Autoimmune Hepatitis and related liver diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03466
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Saitoh Shin-Ichiroh 東京大学, 医科学研究所, 准教授 (90361625)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 樹状細胞 / Rab7a / 自己免疫性肝炎 / 原発性胆汁性胆管炎

Outline of Final Research Achievements

Until now, the pathogenesis of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) has been largely unknown. Much less is known about overlap syndrome, in which both AIH and PBC occur. This is because there is no mouse model of overlap syndrome that develops AIH and PBC. In this study, we clarified that the dendritic cell (DC)-specific Rab7a-deficient mouse produced by the principal investigator is the world's first model mouse that develops such overlap syndrome. We also suggested that endosomal abnormalities in DCs may lead to the development of AIH and PBC through enhanced antigen presentation. This is an unprecedented report on the onset mechanism that endosomal abnormalities in DCs are involved in autoimmune diseases. Furthermore, this is the first report to elucidate that γδT cells are involved in the development of PBC.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

これまでいくつかの自己免疫疾患の発症機構が報告されている。本研究結果では樹状細胞のエンドソーム異常が自己免疫疾患の発症に関与している可能性を新たに示している。今後免疫担当細胞のオルガネラ異常と自己免疫疾患の発症とを結びつける研究が発展して行くものと考えられる。そして免疫細胞にオルガネラ異常が起こる機構に関しても研究を進める必要がある。また本研究結果は全く分かっていなかった自己免疫肝疾患のオーバーラップ症候群の理解に大きな前進となる。さらに原発性胆汁性胆管炎の発症にγδT細胞が関与することが明らかになったことで新規の治療法の開発につながる可能性がある。