Survey of molecular mechanisms for avoiding rejection focusing on the genetic background of liver allograft

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06786
• 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: Kyushu University
• Principal Investigator: Tajima Soichiro 九州大学, 大学病院, 薬剤師 (10579460)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 生体肝移植 / 拒絶反応 / 免疫抑制薬 / 個別化医療 / 免疫寛容

Outline of Final Research Achievements

The development of acute rejection after living-donor liver transplantation (LDLT) often results in fatal liver dysfunction. Therefore, immunosuppression induction therapy in LDLT requires stricter control. In order to overcome rejection in post-liver transplantation immunosuppressive therapy, we searched for a novel molecular mechanism focusing on the genetic background of liver allograft. Focusing on IFR as a candidate molecule involved in individual differences in rejection in LDLT patients, we proceeded with analysis using cytotoxic lymphocytes (NK cells) that play a central role in rejection. As a result, the relationship between IFR and cytotoxic activity of NK cells was shown. Therefore, it was suggested that the expression of IFR in liver allograft reduced the cytotoxic activity of NK cells and may be involved in the avoidance of rejection.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

移植直前のドナー肝を用いた遺伝子発現解析により得られた新しい免疫制御因子としてのIFRに着目し、IFRのNK細胞における細胞傷害活性の抑制作用を明らかにした。臨床的にはIFRが新しい作用機序の画期的な免疫抑制薬の標的分子となりうることが示唆され、IFRの免疫学的意義の詳細な解明によって、多方面への波及効果が期待できる。