Protective Effects of Regulatory T cells in Renal Ischemia-Reperfusion Injury in a Murine Model

Research Project

Project/Area Number	17K16772
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Urology
Research Institution	Akita University
Principal Investigator	YAMAMOTO RYOHEI 秋田大学, 医学部附属病院, 医員 (90770652)
Project Period (FY)	2017-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	虚血再灌流障害 / 制御性T細胞 / 腎虚血再灌流障害 / 虚血再還流障害
Outline of Final Research Achievements	Endogenously expanded-regulatory T cell (Treg) by administration of Trichostatin A　(TsA) contributed to reduce the deterioration in Ischemia/reperfusion injury(IRI) kidney in our murine model. It was associated with suppressed infiltration of inflammatory cells due to the attenuated expression of immune-related antigen molecules after IRI. The key mechanism of this renoprotective effect may be causatively associated with increased IL-10 production and its broad effect on diverseimmune pathways. Tregs expansion by TsA administration may be a new treatment strategy against organ IRI.
Academic Significance and Societal Importance of the Research Achievements	トリコスタチンA（抗真菌剤として臨床的に使われている薬剤）により制御性T細胞を内因性に増幅させることは、細胞を体外に取り出して培養し輸注するという方法よりも簡便でコストが低く、臨床応用し易い。将来的に急性期の腎虚血再灌流障害時にトリコスタチンAを投与することで制御性T細胞を増幅させ腎機能障害を軽減される新しい治療戦略になり得る可能性がある。また、他臓器でも応用可能であると考えている。