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Elucidation of APRIL-mediated immune abnormalities by tonsillar germinal center B cells in the pathogenesis of IgA nephropathy

Research Project

Project/Area Number 17K09713
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionJuntendo University

Principal Investigator

Suzuki Yusuke  順天堂大学, 医学(系)研究科(研究院), 教授 (70372935)

Co-Investigator(Kenkyū-buntansha) 武藤 正浩  順天堂大学, 医学部, 助教 (30790076)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsIgA腎症 / APRIL / 糖鎖異常IgA / 口蓋扁桃 / B細胞 / 免疫異常 / TLR9 / 扁桃 / TACI / BCMA / 粘膜免疫 / 腎臓学
Outline of Final Research Achievements

Previous studies have revealed that IgA antibodies with abnormal glycosylation deposited in the gomerular mesangium in kidney of patients with IgA nephropathy. In recent years, the involvement of a proliferation inducing ligand (APRIL), which is a cytokine involved in the differentiation and survival of plasma cells, has been suggested to be involved in the pathogenesis of IgA nephropathy, however the details have not been clarified. In the present study, we established a culture system that efficiently induces IgA-positive B cells from naive B cells. Using this new culture system, it has become possible to analyze the detailed mechanism by which APRIL produces abnormal glycosilated IgA antibodies.

Academic Significance and Societal Importance of the Research Achievements

IgA腎症の治療において、a proliferation inducing ligand(APRIL)をターゲットとした分子標的治療薬の国際治験が開始され、近年注目されているが、その理論的根拠の詳細は明らかにされていなかった。本研究成果は、口蓋扁桃摘出術、更にはAPRILをターゲットとした分子標的治療薬の理論的根拠や治療適応基準の基礎データ提供につながると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis2018

    • Author(s)
      Suzuki Hitoshi、Yasutake Junichi、Makita Yuko、Tanbo Yuki、Yamasaki Kohei、Sofue Tadashi、Kano Toshiki、Suzuki Yusuke
    • Journal Title

      Kidney International

      Volume: 93 Issue: 3 Pages: 700-705

    • DOI

      10.1016/j.kint.2017.10.019

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA Nephropathy.2017

    • Author(s)
      Muto M, Manfroi B, Suzuki H, Joh K, Nagai M, Wakai S, Righini C, Maiguma M, Izui S, Tomino Y, Huard B, Suzuki Y.
    • Journal Title

      J Am Soc Nephrol

      Volume: 28 Issue: 4 Pages: 1227-1238

    • DOI

      10.1681/asn.2016050496

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Characteristics of naïve B cells in murine IgA Nephropathy and the reconsideration of features of the nephritogenic IgA.2019

    • Author(s)
      二瓶 義人
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Characteristics of B cells in IgA Nephropathy model mice.2019

    • Author(s)
      二瓶 義人
    • Organizer
      Kidney week 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characteristics of naive B cells in murine IgA Nephropathy2018

    • Author(s)
      Nihei Y, Haniuda K, Higashiyama M, Suzuki Y, Kitamura D.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Characteristics of Germinal Center B Cells in Murine IgA Nephropathy2018

    • Author(s)
      Nihei Y, Haniuda K, Suzuki H, Kano T, Fukao Y, Kitamura D, Suzuki Y
    • Organizer
      The 15th International Symposium on IgA Nephropathy
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Aberrantly glycosylated IgA is produced by TLR9 activation through APRIL mediated pathway in IgA nephropathy.2018

    • Author(s)
      Nihei Y
    • Organizer
      ISN FRONTIERS meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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