Tolerance Induction in Organ Transplantation by Myeloid-Derived Suppressor Cells through Recruitment of Regulatory T and B cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18066
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: NAKAMURA TSUKASA 京都府立医科大学, 医学(系)研究科(研究院), 講師 (30777959)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 臓器移植 / 骨髄由来免疫抑制細胞 / 免疫寛容

Outline of Final Research Achievements

Myeloid-derived suppressor cells (MDSCs) are heterogenous myeloid-origin population which potentially suppresses immunological rejection in the field of transplantation.
A recipient C3H mouse received a cardiac graft from a Balb/C mouse. In the untreated group, both class I and II DSA production in serum were confirmed on post-operative days (POD) 10. Upon POD 10, Intra-graft class I DSA deposition was clearly observed, whilst class II DSA started to accumulate. On the other hand, monocytic MDSCs (Ly6G-/Ly6C+/CD11b+) were isolated from the spleens of rapamycin-treated C3H recipient mice on POD 7. These MDSCs were transferred just before reperfusion and on POD 2. As a result, the indices of both class I and II DSA in serum were significantly lower on POD 10. Subsequent intra-graft DSA deposition was also notably suppressed. Taken together, the transfer of MDSCs may postpone DSA production. Consequently, the graft survival was prolonged (8.1±0.9 vs. 24.1±3.8)

Free Research Field

臓器移植

Academic Significance and Societal Importance of the Research Achievements

臓器移植において拒絶反応の制御は最重要課題の一つである。免疫調節能を持つ細胞として制御性T細胞が従来から注目されているが、単独効果での免疫寛容誘導は種々の報告からも難しい可能性がある。一方、近年免疫抑制効果を持つ、MDSCsが免疫抑制、寛容誘導に重要な役割を担っている可能性がある。本研究成果はMDCSsが臓器移植において抗体産生を抑制することを明らかにし、その結果、移植臓器生存期間の延長につながることを示唆した。既存報告と併せ、MDSCsは細胞性拒絶反応、抗体関連型拒絶反応共に制御することを示した。今後、臨床での免疫抑制剤の減量、拒絶反応の治療、また免疫寛容誘導への応用が期待される。