Research on control of innate immunity in the small bowel transplantation

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K20344
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Osaka University
• Principal Investigator: Matsuura Rei 大阪大学, 医学系研究科, 招へい教員 (00747412)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 小腸移植 / 補体 / マクロファージ / 自然免疫

Outline of Final Research Achievements

The rejection of the small intestine is usually very severe and represents a significant immunogenic burden to manage. Therefore, the development of a new immunosuppressive drug with a different suppressive mechanism from Calcineurin inhibitors would be desirable in the field of intestinal transplantation. In this study, we demonstrated that PAK-2 inhibitor/PQA-18 suppresses the function of macrophages and induces a clear immunosuppressive effect via a different mechanism from CNI. We found that PQA-18 clearly prolongs the graft survival in a rat intestinal transplant system. PQA-18 can function efficiently in rat immune cells, and in human ones, by virtue of its ability to suppress not only mixed lymphocyte reactions but macrophage differentiation/ polarization in in vitro and in vivo as well. In addition, it can be assumed that PQA-18 is effective in the suppression of T cell activation in the macrophages-independent manner.

Free Research Field

移植

Academic Significance and Societal Importance of the Research Achievements

移植後の免疫抑制の方法はこれまでリンパ球に主軸を置いて研究されてきた．現在用いられているリンパ球に対する免疫抑制剤の副作用として，腎障害などが知られている．今回，ラット小腸移植モデルにおよび in vitroの実験において、PQA-18のマクロファージを抑制する効果が示された．PQA-18は自然免疫系細胞の抑制による新たな経路での免疫抑制剤である．今後，投与量や副作用の検証を必要とするが，新たな免疫抑制剤となる可能性が示唆された．