Ex Vivo–Induced Bone Marrow-Derived Myeloid Suppressor Cells Prevent Corneal Allograft Rejection in Mice

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16884
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Juntendo University
• Principal Investigator: Fujimoto Keiichi 順天堂大学, 医学部, 助教 (10876684)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨髄由来免疫抑制細胞 / 角膜移植 / 血管新生 / リンパ管新生 / 制御性T細胞 / 免疫寛容 / 炎症 / 免疫

Outline of Final Research Achievements

Bone marrow-derived immunosuppressed cells (BM-MDSCs) were induced by co-culturing bone marrow cells from C57/BL6J mice with IL-6 and granulocyte monocyte colony-stimulating factor (GM-CSF). Addition of BM-MDSCs to the mixed lymphocyte response decreased inflammatory cytokines, increased inhibitory cytokines, suppressed T cell proliferation, and induced regulatory T cells. Subconjunctival injection of BM-MDSCs into corneal allografts prolonged survival and suppressed angiogenesis and lymphangiogenesis, and BM-MDSCs suppressed rejection of murine corneal allografts via the iNOS pathway.

Free Research Field

眼免疫

Academic Significance and Societal Importance of the Research Achievements

本研究は、体外培養した骨髄由来免疫抑制細胞(BM-MDSC)の免疫抑制効果を高リスク角膜移植マウスモデルで検証し、ヒト角膜移植における新規免疫寛容療法開発の基盤研究を実施した。BM-MDSCの混合リンパ球反応への付加により炎症性サイトカインの減少、抑制性サイトカインの増加、T細胞増殖の抑制、制御性T細胞の誘導を認めた。結膜下注射によるBM-MDSCの角膜移植片へ移行ならびに生存率の延長、血管新生ならびにリンパ管新生の抑制を認めた。BM-MDSCは誘導性一酸化窒素合成酵素経路を介したマウス角膜移植片の拒絶反応抑制を示した。