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A role of bone marrow resident-uncommitted NKT cells under the infectious immune responses

Research Project

Project/Area Number 19K16704
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49070:Immunology-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Hayashizaki Koji  東京慈恵会医科大学, 医学部, 助教 (50779907)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsNKT細胞 / 骨髄 / 未分化 / 感染免疫 / 未分化NKT細胞 / 細菌感染 / 肺炎球菌ワクチン
Outline of Research at the Start

肺炎球菌は小児および65歳以上成人の肺炎や髄膜炎の主な原因細菌であることから、より有効なワクチンの開発に繋がる免疫応答の解析は重要である。申請者らのこれまでの研究で、糖脂質をアジュバントとした肺炎球菌ワクチンは従来のワクチンと比較して長期にわたって血中抗体価が維持され感染防御に効果的であることが示唆された。本研究はこの新規ワクチンによって誘導されるエフェクター細胞の分化機序を明らかにし、感染防御における重要性を明らかにすることを目的としている。本研究成果は、より効果的なワクチン法の樹立に貢献することが期待される。

Outline of Final Research Achievements

NKT cells acquire the effector function during thymic development and thus rapidly produce high amount of cytokine under activation. A previous report suggested that peripheral NKT pool contains “uncommitted NKT cells” which differentiate into functional subsets depending on the environment. However, the detail about uncommitted NKT cells still remain unknown. In this study, we have focused on bone marrow (BM)-resident NKT cells which be expected to carry the uncommitted potential, and analyzed for specific marker and function. Although our project has been difficult because BM-NKT cells more highly sensitive for the environment change, we could successfully gain several data which lead to the elucidate for physiological importance of uncommitted NKT cells.

Academic Significance and Societal Importance of the Research Achievements

NKT細胞は活性化に伴い迅速かつ多量のサイトカインを産生することで強力な免疫不活化作用をもつ。このことから、抗腫瘍免疫の分野や感染症ワクチン分野における臨床応用に注目が集まっている。本研究で詳細に解析を進めた骨髄NKT細胞の未分化能についての解析結果は、未分化な状態での末梢NKT細胞の維持や増殖手法の手がかりになることが期待され、治験やトランスレーショナル研究として推進されているNKT細胞研究を強くサポートする。よって当研究は学術的にも社会的にも有意義な成果を残すことができたといえる。

Report

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

    (11 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results) Book (2 results)

  • [Journal Article] Acsbg1-dependent mitochondrial fitness is a metabolic checkpoint for tissue Treg cell homeostasis2021

    • Author(s)
      Kanno Toshio、Nakajima Takahiro、Kawashima Yusuke、Yokoyama Satoru、Asou Hikari K.、Sasamoto Shigemi、Hayashizaki Koji、Kinjo Yuki、Ohara Osamu、Nakayama Toshinori、Endo Yusuke
    • Journal Title

      Cell Reports

      Volume: 37(6) Issue: 6 Pages: 109921-109921

    • DOI

      10.1016/j.celrep.2021.109921

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SCD2-mediated monounsaturated fatty acid metabolism regulates cGAS-STING-dependent type I IFN responses in CD4+ T cells2021

    • Author(s)
      Kanno Toshio、Nakajima Takahiro、Yokoyama Satoru、Asou Hikari K.、Sasamoto Shigemi、Kamii Yasuhiro、Hayashizaki Koji、Ouchi Yasuo、Onodera Taishi、Takahashi Yoshimasa、Ikeda Kazutaka、Hasegawa Yoshinori、Kinjo Yuki、Ohara Osamu、Nakayama Toshinori、Endo Yusuke
    • Journal Title

      Communications Biology

      Volume: 4(1) Issue: 1 Pages: 820-820

    • DOI

      10.1038/s42003-021-02310-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Myosin Light Chain 9/12 Regulates the Pathogenesis of Inflammatory Bowel Disease2021

    • Author(s)
      Yokoyama Masaya、Kimura Motoko Y.、Ito Toshihiro、Hayashizaki Koji、Endo Yukihiro、Wang Yangsong、Yagi Ryoji、Nakagawa Tomoo、Kato Naoya、Matsubara Hisahiro、Nakayama Toshinori
    • Journal Title

      Frontiers in Immunology

      Volume: 11

    • DOI

      10.3389/fimmu.2020.594297

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] NKT-mediated vaccine induces affinity maturation of BCR and supply antibody dependent protection against Streptococcus pneumoniae2021

    • Author(s)
      Koji Hayashizaki
    • Organizer
      第50回日本免疫学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Pneumococcal surface protein A and glycolipid vaccine augments generation of long-lived plasma cells that produce antigen-specific IgG2021

    • Author(s)
      Koji Hayashizaki
    • Organizer
      第3回アジア肺炎球菌シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 糖脂質アジュバントで誘導される濾胞性ヘルパーNKT細胞の分化機構の解明2021

    • Author(s)
      林﨑 浩史
    • Organizer
      第6回糖鎖免疫研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規肺炎球菌ワクチンの免疫学的作用機序の解析2020

    • Author(s)
      林﨑浩史、高塚翔吾、川久保俊、竹山春子、川上和義、大石和徳、宮崎義継、金城雄樹
    • Organizer
      第31回日本生体防御学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] The protein and glycolipid vaccine induce long-term protection against pneumococcal infection through differentiation of follicular helper NKT cells.2019

    • Author(s)
      Hayashizaki K, Takatsuka S, Kawakubo S, Kamii Y, Takahashi Y, Kawakami K, Kubo M, Kinjo Y.
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Research-status Report
  • [Presentation] 糖脂質アジュバントを用いた肺炎球菌ワクチンの抗体産生誘導及び感染防御機構の解明2019

    • Author(s)
      林﨑 浩史、高塚 翔吾、川久保 俊、大石 和徳、宮﨑 義継、金城 雄樹
    • Organizer
      第30回日本生体防御学会学術総会
    • Related Report
      2019 Research-status Report
  • [Book] 呼吸器内科2021

    • Author(s)
      林﨑 浩史, 上井 康寛, 桑野 和善, 金城 雄樹
    • Total Pages
      6
    • Publisher
      科学評論社
    • Related Report
      2021 Annual Research Report
  • [Book] 食品免疫学事典2021

    • Author(s)
      日本食品免疫学会
    • Total Pages
      492
    • Publisher
      朝倉書店
    • ISBN
      9784254431261
    • Related Report
      2021 Annual Research Report

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

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