Establishment of a therapeutic method to induce Treg through steroid receptor in organ transplantation.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08540
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Hiroshima University
• Principal Investigator: Tanaka Yuka 広島大学, 医系科学研究科(医), 准教授 (90432666)
• Co-Investigator(Kenkyū-buntansha): 大段 秀樹 広島大学, 医系科学研究科(医), 教授 (10363061)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 制御性T細胞 / ステロイド / 臓器移植 / 遺伝子多型

Outline of Final Research Achievements

Steroids are routinely widely used in the treatment of various pathological conditions such as inflammation and autoimmune diseases, but they have many side effects and the mechanism of action is still unclear. It is also widely used in organ transplantation as a preventive agent for rejection and a therapeutic agent for acute cellular rejection (ACR). However, the effect varies from individual to individual, and 20 to 50% of ACR shows steroid pulse resistance.
Regulatory T cells (Tregs) control the overreaction of anti-donor responsive T cells in organ transplants. In this study, we analyzed steroid sensitivity by gene polymorphism of FOXP3, which is a master gene of Treg cells, and analyzed its involvement in organ transplantation. As a result, it was obtained that FOXP3-SNP may be related to the association with the onset of postoperative DSA.

Free Research Field

移植免疫

Academic Significance and Societal Importance of the Research Achievements

臓器移植後の拒絶反応の治療には、ステロイドパルスが第一選択として用いられる。移植以外の分野でもステロイドパルス療法は、その免疫抑制効果から経験的に使用されてきたが、
免疫機構に対しての明らかなエビデンスは不明な点が多い。ステロイドレセプターを介した制御性T細胞の誘導・機能変化が明らかになれば、臓器移植のみならず自己免疫疾患、癌治療など制御性T細胞が関与する様々な病態において非特異的ステロイド療法に代わる新規治療法の開発へつながることが予測される。