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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 TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionOsaka 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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Temporal and spatial profile of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in ischemic stroke in mice2019

    • Author(s)
      Kawano T, Shimamura M, Nakagami H, Kanki H, Sasaki T, Mochizuki H.
    • Journal Title

      PLOS ONE

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳梗塞におけるPMN-MDSCの経時的および空間的発現解析2019

    • Author(s)
      河野友裕、島村宗尚 他
    • Organizer
      第44回日本脳卒中学会学術集会
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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