Attenuation of lung graft dysfunction induced by the inappropriate activation of innate immunity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03769
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kyoto University
• Principal Investigator: Tanaka Satona 京都大学, 医学研究科, 助教 (80847517)
• Co-Investigator(Kenkyū-buntansha): 伊達 洋至 京都大学, 医学研究科, 教授 (60252962)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肺移植 / 虚血再灌流肺障害 / 抗炎症性脂質メディエーター / 自然免疫 / 拒絶反応

Outline of Final Research Achievements

In this study, we focused on specialized pro-resolving mediators, which have been reported to resolve inflammation in various disease model. Dynamics of SPMs in the initiation and resolution process of pulmonary ischemia-reperfusion injury was investigated and reported. AT-RvD1 and AT-LXA4 attenuated pulmonary ischemia-reperfusion injury in rat hilar clamp model. This effect of AT-RvD1 and AT-LXA4 was considered as a process mediated by FPR2 receptor. Moreover, mouse model of orthotopic lung transplantation was established to investigate an impact of pro-inflammatory or anti-inflammatory event early after transplantation on long-term graft function. We also conducted retrospective clinical study to evaluate whether inflammatory events early after transplantation affect long-term patient outcome.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

手術技術、周術期管理、免疫抑制剤の発展により、心臓や肝臓など固形臓器移植は80％以上の5年生存率が達成されているが、肺移植においては、国際学会のレジストリーで報告される5年生存率はいまだ50％程度で、長期予後は不良である。本研究では、虚血再灌流肺障害における抗炎症性脂質メディエーターの動態と介入効果を示し、それらが移植肺の機能に与える影響を検討する実験モデルと臨床研究基盤を確立した。肺移植患者の予後改善のため、さらなる研究発展が期待できる。