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Elucidation of unique characteristics of renal fibroblasts in fibrosis

Research Project

Project/Area Number 17K19550
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pathology, Infection/Immunology, and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Kurashima Yosuke  東京大学, 医科学研究所, 特任准教授 (30729372)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords線維化 / 線維芽細胞 / マスト細胞 / コラーゲン / マクロファージ / 慢性炎症 / 腎尿細管間質線維化 / 筋線維芽細胞 / ミエロイド細胞 / 細胞外マトリックス / 慢性腎不全 / ミエロイド系細胞 / 抗線維化抗体 / 慢性腎臓病 / 腎線維化
Outline of Final Research Achievements

Excessive accumulation of extracellular matrix such as type I collagen induced fibrosis and eventually causing organ failure. In kidney, renal interstitial fibrosis is a common pathology when chronic kidney disease was aggravated. However, the underlined mechanisms of kidney fibrosis especially interstitial fibrosis have not been well elucidated. We newly found unique myeroid cell populations, which are capable of producing collagen, are increased in the fibrotic kidney. Those myeroid cell populations are induced by fibrogenic renal fibroblasts in vitro. Importantly, those fibrogenic fibroblasts are increased by activation of mast cells. Taken together, the triangular interaction of those cellular populations could be a major pathological event for renal fibrotic disease and considered as a new drug target.

Academic Significance and Societal Importance of the Research Achievements

本課題はこれまで申請者が取り組んできた、生体恒常性維持のための「線維芽細胞―免疫細胞相互作用」についての研究成果から着想を進めた研究課題である。本研究から、コラーゲンを選択的に産生し、線維化促進に働くミエロイド系細胞を見出し、この細胞の誘導プロセスから腎線維芽細胞の特殊性や新たな活性化機序が明らかになった新規性・独自性の高い研究として位置付けられる。
「組織特異的な病原性線維芽細胞による線維化誘導機構」という新しいコンセプトの立証に繋がると考えられ、病原性線維芽細胞を標的とした新規治療につながる成果である。

Report

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

    (19 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 9 results) Book (1 results)

  • [Journal Article] Distinct Roles for Peyer’s Patch B Cells for Induction of Antigen-specific IgA Antibody Responses in Mice Administered Oral Recombinant Salmonella2019

    • Author(s)
      Hashizume-Takizawa Tomomi、Shibata Naoko、Kurashima Yosuke、Kiyono Hiroshi、Kurita-Ochiai Tomoko、Fujihashi Kohtaro
    • Journal Title

      International Immunology

      Volume: - Issue: 8 Pages: 531-541

    • DOI

      10.1093/intimm/dxz029

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A comprehensive understanding of the gut mucosal immune system in allergic inflammation2019

    • Author(s)
      Tokuhara Daisuke、Kurashima Yosuke、Kamioka Mariko、Nakayama Toshinori、Ernst Peter、Kiyono Hiroshi
    • Journal Title

      Allergology International

      Volume: 68 Issue: 1 Pages: 17-25

    • DOI

      10.1016/j.alit.2018.09.004

    • NAID

      130007557958

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ATP as a Pathophysiologic Mediator of Bacteria-Host Crosstalk in the Gastrointestinal Tract2018

    • Author(s)
      Inami Akie、Kiyono Hiroshi、Kurashima Yosuke
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 8 Pages: 2371-2371

    • DOI

      10.3390/ijms19082371

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] in vitro腸管マルチエコシステム解析から見えてきた腸内細菌-上皮-免疫クロストークの多様性2018

    • Author(s)
      山本 智久, 清野 宏, 倉島 洋介
    • Journal Title

      腎臓内科・泌尿器科 = Nephrology & urology

      Volume: 7 Pages: 613-618

    • NAID

      40021606608

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Eosinophil depletion suppresses radiation-induced small intestinal fibrosis.2018

    • Author(s)
      Takemura N, Kurashima Y, Mori Y, Okada K, Ogino T, Osawa H, Matsuno H, Aayam L, Kaneto S, Park EJ, Sato S, Matsunaga K, Tamura Y, Ouchi Y, Kumagai Y, Kobayashi D, Suzuki Y, Yoshioka Y, Nishimura J, Mori M, Ishii KJ, Rothenberg ME, Kiyono H, Akira S, Uematsu S.
    • Journal Title

      Sci Transl Med.

      Volume: -- Issue: 429 Pages: 264-273

    • DOI

      10.1126/scitranslmed.aan0333

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mucosal Mesenchymal Cells: Secondary Barrier and Peripheral Educator for the Gut Immune System2017

    • Author(s)
      Kurashima Yosuke、Yamamoto Daiki、Nelson Sean、Uematsu Satoshi、Ernst Peter B.、Nakayama Toshinori、Kiyono Hiroshi
    • Journal Title

      Front. Immunol.

      Volume: 8 Pages: 1787-1787

    • DOI

      10.3389/fimmu.2017.01787

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腸管粘膜・皮膚などにおける上皮-間葉-神経系ネットワークによる末梢免疫教育機構2018

    • Author(s)
      倉島 洋介
    • Organizer
      アステラス製薬株式会社
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Purinergic Regulation of Mast Cells for Symbiosis and Elimination2018

    • Author(s)
      倉島 洋介
    • Organizer
      第55回日本消化器免疫学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mesenchymal cells: Secondary barrier and peripheral educator for the immune system2018

    • Author(s)
      倉島 洋介
    • Organizer
      第20回千葉大学テニュアトラックセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 間葉系細胞による免疫恒常性維持機構2018

    • Author(s)
      倉島 洋介
    • Organizer
      第8回オルソオルガノジェネシス検討会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Bringing mast cells over to our side to overcome allergy2018

    • Author(s)
      倉島 洋介
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 間葉系細胞による免疫末梢教育2018

    • Author(s)
      倉島 洋介
    • Organizer
      第42回日本リンパ学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mesenchymal cell-mediated local inflammatory loop in intestinal inflammation2018

    • Author(s)
      倉島 洋介
    • Organizer
      2nd Korea-Japan Joint Meeting on Mucosal Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] 共生と排除を司る粘膜マスト細胞の研究2018

    • Author(s)
      倉島 洋介
    • Organizer
      第22回腸内細菌学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mast cell and mesenchymal cell regulate immunity and inflammation2018

    • Author(s)
      Kurashima Y.
    • Organizer
      The Inaugural Chiba University-UCSD Symposium on Mucosal Immunology, Allergy and Vaccines: Impact on Mucosal Diseases and Global Health
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mesenchymal cells as a peripheral educator for immunity and inflammation2018

    • Author(s)
      Kurashima Y.
    • Organizer
      1st Gut Bio Society Workshop Grand Intercontinental Seoul, Seoul, Korea
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mesenchymal-myeloid cell interactions in renal microenvironment for pathological fibrogenic machinery in kidney fibrosis2017

    • Author(s)
      Kurashima Y., Kiyono H.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Mesenchymal-mediated skin-specific regulatory system for the control of tissue resident mast cells2017

    • Author(s)
      Kogure Y., Kurashima Y, et al.,
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Book] 免疫生物学(原書第9版)2019

    • Author(s)
      笹月 健彦、吉開 泰信
    • Total Pages
      910
    • Publisher
      南江堂
    • ISBN
      9784524251155
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2017-07-21   Modified: 2020-03-30  

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