The mechanism of acute liver failure focusing on immune response and cell-cell interacition

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15976
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kyushu University
• Principal Investigator: Kuwano Akifumi 九州大学, 医学研究院, 共同研究員 (90899006)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 急性肝不全 / 免疫応答

Outline of Final Research Achievements

To uncover the pathogenesis of acute liver failure (ALF) with microcirculatory disturbance, I analyzed Concanavalin A mouse model which presented ALF with microcirculatory disturbance. In this model, IFNγ was upregulated in innate lymphoid cells and stimulated hepatic vascular endothelial cells at the early stage of liver injury. IFNγ upregulated CD40 expression and Tissue factor (TF) was further induced by increased CD40-CD40 ligand interaction. These mechanism of the IFNγ-CD40-TF axis were involved in microcirculatory disturbance in human ALF patients.

Free Research Field

急性肝不全

Academic Significance and Societal Importance of the Research Achievements

急性肝不全は肝移植以外に有効な治療法が確立されておらず、移植治療ができない場合の致命率は高い。肝移植は脳死移植におけるドナー不足の問題、生体肝移植は健常者への手術侵襲の問題があり、移植以外の治療法の開発が望まれている。今回同定したIFNγ-CD40-TF axisのメカニズムはヒトの急性肝不全の発症にも関与しているものと考えられ、急性肝不全の内科的な新たな治療法の開発のターゲットとなりえる。本研究で得られた知見は急性肝不全の新たな治療戦略の開発へと繋がる基盤的な知見であると考えている。