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The role of neutrophil extracellular traps in the pathogenesis of chronic GVHD

Research Project

Project/Area Number 18K08353
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKyoto University

Principal Investigator

Yamashita Kouhei  京都大学, 医学研究科, 准教授 (80402858)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords好中球細胞外トラップ / 移植片対宿主病 / 川崎病 / 炎症性疾患 / 自然免疫 / PAD阻害薬 / シトルリン化ヒストン / 血管炎 / 血管障害 / 慢性GVHD / 形質細胞様樹状細胞 / Ⅰ型インターフェロン / 慢性移植片対宿主病 / 同種移植 / 免疫寛容
Outline of Final Research Achievements

Neutrophil extracellular traps (NETs), a novel extracellular killing mechanism of neutrophils, are involved in the pathogenesis of immune, inflammatory, or thrombotic diseases, due to harmful proteins such as histone and anti-microbial peptides, released extracellularly from neutrophils. In this study, we revealed an important role of NETs, at least in part, in the pathogenesis of chronic GVHD, one of the serious complications after allogeneic hematopoietic cell transplantation, or Kawasaki disease, one of the representative systemic vascular inflammatory diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究において、代表的な炎症性疾患の一つである川崎病における血管炎病変の形成にNETsが重要な役割を果たすことを、疾患モデルマウスや患者検体を用いた解析により明らかにした。本研究遂行時、COVID-19関連川崎病類似疾患(小児多系統炎症性症候群:MIS-C)が欧米を中心に報告され、MIS-Cと古典的川崎病との関係について、トピックスとなった。今回明らかにした所見から、MIS-Cと古典的川崎病は病態を共有しており、MIS-Cはその重症型である、という仮説を立て、報告した(Ann Rheum Dis, 2020)。他の研究者からも我々の仮説の妥当性が示され、MIS-Cの理解が進んだ。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2020

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

  • [Journal Article] Exaggerated neutrophil extracellular trap formation in Kawasaki disease: A key phenomenon behind the outbreak in western countries?2020

    • Author(s)
      Yamashita K, Takaori-Kondo A, Mizugishi K.
    • Journal Title

      Ann Rheum Dis

      Volume: Aug 21 Issue: 9 Pages: 2020-218593

    • DOI

      10.1136/annrheumdis-2020-218593

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

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