Therapeutic effect of plasmacytoid dendritic cells transplantation for acute liver failure

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21607
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Keio University
• Principal Investigator: Nakamoto Nobuhiro 慶應義塾大学, 医学部(信濃町), 准教授 (40383749)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 急性肝不全 / 樹状細胞

Outline of Final Research Achievements

Plasmacytoid dendritic cells (pDCs) perform dual pro-inflammatory and immunosuppressive roles. We recently reported the potential of pDC therapy for treatment of intractable acute liver failure. However, establishment of efficient methods to deliver pDCs to the liver is essential for future clinical therapeutic applications. The present study demonstrates a higher abundance of liver and peripheral blood pDCs in mice lacking the C-C motif chemokine receptor 9 (CCR9), a pDC gut-homing receptor, than that in WT mice. Adoptive pDC transfer resulted in a higher efficiency of Ccr9-/- pDC migration to the liver than that to the original target organ, the small intestine as compared to WT pDCs. Further, Ccr9-/- pDCs consistently migrated efficiently to the concanavalin A induced inflamed liver, and exerted a more effective immunosuppressive effect, resulting in better protection against acute liver inflammation than that demonstrated by WT pDCs.

Free Research Field

肝臓免疫

Academic Significance and Societal Importance of the Research Achievements

急性肝不全は非常に致死率が高く、欧米では第一選択の治療法として肝移植が選択されるが、本邦では圧倒的なドナー不足の問題を抱えており、内科的治療の進歩が喫緊の課題である。本研究は従来肝臓の自己再生、肝臓移植までのブリッジング治療として行われてきた人工肝臓補助、副腎皮質ストロイドを用いた急性肝不全に対する内科治療の治療体系を変革する可能性がある挑戦的研究である。実臨床における実現性の点においては今後解明すべき課題があるが、ヒト臨床サンプル、モデルマウスの検討に基づく研究成果であり今後のさらなる前進が期待され、本研究成果が社会に与える影響力も大きい。