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A novel regulatory mechanism for innate immune signals by ectoenzymes BST-1 and CD38

Research Project

Project/Area Number 19K08943
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionKawasaki Medical School

Principal Investigator

Iseki Masanori  川崎医科大学, 医学部, 講師 (30532353)

Co-Investigator(Kenkyū-buntansha) 石原 克彦  川崎医科大学, 医学部, 教授 (10263245)
矢作 綾野  川崎医科大学, 医学部, 助教 (10584873)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords辺縁帯B細胞 / マクロファージ / IL-6 / 抗体産生 / 自然免疫 / 細胞膜外酵素 / B細胞 / TLR
Outline of Research at the Start

細胞膜外酵素BST-1 (CD157)は、CD38と共にADPリボシルシクラーゼ酵素のファミリーを形成している。しかし我々の身体の中でどのような働きをしているのかは分かっていない。我々はBST-1遺伝子欠損マウス(Bst1KO)の解析から、BST-1、CD38が大腸菌感染の際のB細胞やマクロファージの反応を制御している可能性があるという実験データを得た。本研究ではBST-1/CD38による新しい免疫制御機構を解明し、感染や炎症性疾患の発症にどのように関係するか、病気の治療や診断に使えるかについて調べていく。

Outline of Final Research Achievements

We have been clarifying that an ectoenzyme BST-1 is expressed on various immune cells. To uncover its function in vivo, we generated BST-1 gene deficient mice and analyzed their responses against antigen immunization or challenge of microbial component, LPS. Experiments were done in specific pathogen-free condition with strict experimental conditions for keeping out environmental and other effects. As a result, there was no significant differences in antibody production against thymus-independent antigens and endotoxin shock induced by LPS injection. These results indicate that BST-1 is not required for these innate-like immune responses.

Academic Significance and Societal Importance of the Research Achievements

我々は予備実験においてBST-1遺伝子欠損マウスはB細胞を直接活性化できる外来抗原に対する反応が亢進しているという結果を得ていた。しかしながら動物の飼育条件や比較対照動物の選定を厳密にしてもう一度実験を行ったところ、通常のマウスと変異マウスの間で有意な反応の差は見られなかった。免疫反応は個体が生育、居住する環境から多くの影響を受ける。動物を用いて免疫反応を調べる際はそれらの条件を厳密に揃えることが正しい結果を得るために重要である。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Imatinib has minimal effects on inflammatory and osteopenic phenotypes in a murine cherubism model2021

    • Author(s)
      Mukai Tomoyuki、Akagi Takahiko、Hiramatsu Asano Sumie、Tosa Ikue、Ono Mitsuaki、Kittaka Mizuho、Ueki Yasuyoshi、Yahagi Ayano、Iseki Masanori、Oohashi Toshitaka、Ishihara Katsuhiko、Morita Yoshitaka
    • Journal Title

      Oral Diseases

      Volume: - Issue: 3 Pages: 0-0

    • DOI

      10.1111/odi.14073

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct physical condition and social behavior phenotypes of CD157 and CD38 knockout mice during aging.2020

    • Author(s)
      2.Maria Gerasimenko; Olga Lopatina; Anna A. Shabalova; Stanislav M. Cherepanov; Alla B. Salmina; Shigeru Yokoyama; Hisanori Goto; Hiroshi Okamoto; Yasuhiko Yamamoto; Katsuhiko Ishihara; Haruhiro Higashida.
    • Journal Title

      PLoS One

      Volume: 15(12) Issue: 8 Pages: 4169-4169

    • DOI

      10.3390/ijms22084169

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional analysis of a novel G87V TNFRSF1A mutation in patients with TNF receptor-associated periodic syndrome2019

    • Author(s)
      Tsuji, S. Matsuzaki, H. Iseki, M. Nagasu, A. Hirano, H. Ishihara, K. Ueda, N. Honda, Y. Horiuchi, T. Nishikomori, R. Morita, Y. Mukai, T.
    • Journal Title

      Clin Exp Immunol

      Volume: 198 Issue: 3 Pages: 416-429

    • DOI

      10.1111/cei.13365

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production2019

    • Author(s)
      Yang Qianting、Liao Mingfeng、Wang Wenfei、Zhang Mingxia、Chen Qi、Guo Jiubiao、Peng Bin、Huang Jian、Liu Haiying、Yahagi Ayano、Xu Xingzhi、Ishihara Katsuhiko、Cooper Andrea、Chen Xinchun、Cai Yi
    • Journal Title

      mBio

      Volume: 10 Issue: 4

    • DOI

      10.1128/mbio.01949-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IL-6-PAD4 axis in the earliest phase of arthritis in knock-in gp130F759 mice, a model for rheumatoid arthritis2019

    • Author(s)
      Yahagi Ayano、Saika Taro、Hirano Hiroyasu、Takai-Imamura Miwa、Tsuji Fumio、Aono Hiroyuki、Iseki Masanori、Morita Yoshitaka、Igarashi Hideya、Saeki Yukihiko、Ishihara Katsuhiko
    • Journal Title

      RMD Open

      Volume: 5 Issue: 2 Pages: e000853-e000853

    • DOI

      10.1136/rmdopen-2018-000853

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice2019

    • Author(s)
      Nagasu Akiko、Mukai Tomoyuki、Iseki Masanori、Kawahara Kyoko、Tsuji Shoko、Nagasu Hajime、Ueki Yasuyoshi、Ishihara Katsuhiko、Kashihara Naoki、Morita Yoshitaka
    • Journal Title

      Cells

      Volume: 8 Issue: 5 Pages: 402-402

    • DOI

      10.3390/cells8050402

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] The investigation of the pathogenesis of TNF Receptor-Associated Periodic Syndrome (TRAPS) using murine TRAPS models2021

    • Author(s)
      赤木貴彦, 向井知之, 浅野澄恵, 井関將典, 矢作綾野, 平野紘康, 中野和久, 石原克彦, 守田吉孝
    • Organizer
      The 50th Annual Meeting of the Japanese Society for Immunology(JSI2021)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Lack of bone marrow stromal cell antigen-1 (BST-1)/CD157 ameliorated colitis induced by dextran sodium sulfate (DSS)2021

    • Author(s)
      Katsuhiko Ishihara, Ayano Yahagi, Ryo Katsumata, Akiko Shiotani, Masanori Iseki
    • Organizer
      VIRTUAL IMMUNOLOGY2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 関節リウマチモデルgp130F759の最初期滑膜細胞のシングルセルRNA-seq解析2021

    • Author(s)
      矢作 綾野、井関 將典、石原 克彦
    • Organizer
      第65回日本リウマチ学会総会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] BST-1/CD157の欠損による滑膜線維芽細胞のIL-6産生低下により、GP130F759の関節炎における線維化が軽減した。2020

    • Author(s)
      石原 克彦, 矢作 綾野, 井関 將典
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] BST-1/CD157はDSS誘発性大腸炎における腸上皮の傷害を促進させる2020

    • Author(s)
      矢作 綾野、井関 將典、石原 克彦
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 関節リウマチモデルgp130F759の最初期病変におけるIL-6-PAD4連関2020

    • Author(s)
      矢作 綾野、井関 將典、石原 克彦
    • Organizer
      第64回日本リウマチ学会総会・学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Toll-like receptor-induced Ab production from marginal zone B cells is negatively regulated by ADP-ribosyl cyclase BST-1/CD1572019

    • Author(s)
      Masanori Iseki, Ayano Yahagi, Katsuhiko Ishihara
    • Organizer
      The 48th Annual Meeting of the Japanese Society for Immunology
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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