Clarification of roles of myeloid-derived suppressor cells on the regulation of post-ischemic inflammation

Research Project

Project/Area Number	16K10720
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Neurosurgery
Research Institution	Osaka University
Principal Investigator	Shimamura Munehisa 大阪大学, 医学系研究科, 寄附講座准教授 (60422317)
Co-Investigator(Kenkyū-buntansha)	栗波仁美大阪大学, 医学部附属病院, 助教 (10638555)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	骨髄由来免疫抑制細胞 / 脳梗塞 / 炎症 / 脳血管障害学
Outline of Final Research Achievements	Although T cells play important roles in the pathophysiology of ischemic stroke, the dynamics of T cells remains unclear. Therefore, we examined the temporal and spatial profiles of PMN-MDSCs, which suppress T cells activation. The number of CD11b+Ly6ClowLy6G+ cells was increased in the ischemic hemisphere and bone marrow at 72 hours, as well as in the spleen 24 hours after ischemic stroke in mice. CD11b+Ly6ClowLy6G+ cells sorted from brain and spleen 72 hours after ischemia had greater expression of Nox2 and CHOP mRNA than neutrophils in bone marrow, suggesting that these cells constitute PMN-MDSCs. CD11b+Ly6G+ cells were located in the ischemic core and border zone, indicating that PMN-MDSCs might be endemic to these regions. Although neutrophils are believed to invade infarct regions, the present study suggested that some of these cells are PMN-MDSCs.
Academic Significance and Societal Importance of the Research Achievements	脳梗塞においてT細胞による細胞性免疫は脳虚血24時間以降のlateフェーズでの炎症や組織障害に関与しているが、T細胞の動態制御については明らかとなっていなかった。本検討により、癌免疫においてT細胞の機能を制御することが報告されているPMN-MDSCが、脳梗塞部位においてもT細胞が発現してくるタイミングで発現してくることが明らかとなったことから、癌と同じように、PMN-MDSCをターゲットにしたT細胞制御による新たな脳梗塞治療の可能性につながる可能性が見いだされた点に意義がある。