Regulatory T cells and drug-induced liver injury in type 2 diabetes

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Teikyo Heisei University
• Principal Investigator: HAMADA Kazuma 帝京平成大学, 薬学部, 准教授 (90596884)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 2型糖尿病 / 脂肪肝 / 薬物性肝障害 / ミトコンドリア / 肝免疫環境 / オミクス解析

Outline of Final Research Achievements

Alterations in immune responsiveness associated with various diseases and pathological conditions are important host factors, alongside genetic predispositions, in understanding the susceptibility and mechanisms of idiosyncratic drug toxicities. This study utilized a type 2 diabetes fatty liver model to investigate the liver immune environment. The results indicate that self-derived molecules involved in immune responses leaking from mitochondria in response to a hepatotoxic compound differ between diabetic and non-diabetic states. Furthermore, immunological differences in gene expression profiles of diabetic liver tissue were observed. These findings highlight the immunological background as a key factor in explaining the host susceptibility to drug-induced liver injury in type 2 diabetes.

Free Research Field

代謝免疫学、システム毒性学

Academic Significance and Societal Importance of the Research Achievements

疾患・病態という宿主因子を免疫応答性の相違と捉え、2型糖尿病脂肪肝における免疫環境をオミクスデータに基づく生命情報科学的手法を用いた解析を導入して明らかとした。特に不明な点が多い肝毒性初期免疫応答としてミトコンドリアを起点とした肝細胞応答に迫った。得られた成果は肝毒性応答の全体像をシステムとして包括的に理解することにつながり、肝免疫に着目した肝障害回避、予測、治療戦略開発に加え、ライフスタイル変化に伴い世界中で増加している脂肪性肝疾患の分子病態解明、創薬標的同定、それら研究領域の技術創出に知見を与えるものである。