Ex vivo-induced bone marrow-derived myeloid suppressor cells prevent corneal allograft rejection in mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22985
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Juntendo University
• Principal Investigator: Fujimoto Keiichi 順天堂大学, 医学部, 非常勤助手 (10876684)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: 角膜移植 / 骨髄由来免疫抑制細胞 / 制御性T細胞 / 免疫寛容 / 血管新生 / リンパ管新生

Outline of Final Research Achievements

This study examined the immunosuppressive effects of in vitro cultured bone marrow-derived immunosuppressive cells (BM-MDSCs) in a murine high-risk corneal transplantation model. 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 showed corneal graft migration of BM-MDSC, prolonged graft survival, suppressed angiogenesis and lymphangiogenesis. BM-MDSCs have been shown to inhibit rejection of murine corneal transplantation by suppressing T cell proliferation, inducing regulatory T cells, and inhibiting vascular and lymphangiogenesis via the iNOS pathway.

Free Research Field

角膜移植免疫

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iNOS経路を介して、T細胞増殖の抑制、制御性T細胞の誘導、血管・リンパ管新生の抑制によりマウス角膜移植の拒絶反応を抑制を明らかにした。