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Immunosuppressive function of unsaturated fatty acid produced by lactic acid bacteria.

Research Project

Project/Area Number 19K05884
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionOsaka University (2021)
Tokyo University of Science (2019-2020)

Principal Investigator

Yashiro Takuya  大阪大学, 医学系研究科, 助教 (00726482)

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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords乳酸菌 / 不飽和脂肪酸 / 免疫抑制 / 自己免疫疾患 / 樹状細胞 / T細胞 / エノン脂肪酸 / γ-オキソ脂肪酸 / アレルギー
Outline of Research at the Start

近年、多価不飽和脂肪酸の一部は腸内に生息する乳酸菌によって飽和化され、その過程で合成される中間体には生体調節機能があることが明らかになってきた。申請者はこれら中間体の免疫調節機能を解析した結果、γ-オキソ脂肪酸と呼ばれるグループに免疫抑制作用があることを見出した。本研究ではγ-オキソ脂肪酸の応答細胞を同定し、そこから作用機序を解明する。また、アレルギーや自己免疫疾患のモデル動物を用いてγ-オキソ脂肪酸の摂取が症状を改善できるかについて検証することで免疫疾患に対する予防効果を示していく。さらには、ヒトの免疫細胞に対してもγ-オキソ脂肪酸が免疫抑制作用を示すかについて検証する。

Outline of Final Research Achievements

Lactic acid bacteria living in the gut saturate diet-derived polyunsaturated fatty acids through a unique pathway. In this study, we found that enone fatty acids, one of the intermediates of PUFA metabolism by lactic acid bacteria, possess immunosuppressive effects in vitro experiments. In addition, we also demonstrated that intake of enone fatty acids suppressed the onset of autoimmune diseases, suggesting that enone fatty acids exert immunosuppressive properties in vivo.

Academic Significance and Societal Importance of the Research Achievements

生活習慣病予防の観点から脂質の摂取は極力控える方が良いとされてきたが、最近の研究の進展により、脂質の中にも「良い脂質」と「悪い脂質」があることが報告されてきており、一概に忌避すべきものではないとの見方が広がっている。本研究が示したように、不飽和脂肪酸の乳酸菌代謝物には免疫疾患を予防する効果があることから、脂質の摂取とともに乳酸菌を摂取することで「より良い脂質」が腸内で生成されることが明らかとなり、食生活に新たな概念をもたらす研究成果となった。

Report

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

    (14 results)

All 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] PU.1 regulates Ccr7 gene expression by binding to its promoter in na?ve CD4 + T cells2020

    • Author(s)
      Yashiro Takuya、Takeuchi Hiromi、Kasakura Kazumi、Nishiyama Chiharu
    • Journal Title

      FEBS Open Bio

      Volume: 10 Issue: 6 Pages: 1115-1121

    • DOI

      10.1002/2211-5463.12861

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual Roles of PU.1 in the Expression of PD-L2: Direct Transactivation with IRF4 and Indirect Epigenetic Regulation2020

    • Author(s)
      Inaba Keito、Yashiro Takuya、Hiroki Ikumi、Watanabe Ryosuke、Kasakura Kazumi、Nishiyama Chiharu
    • Journal Title

      The Journal of Immunology

      Volume: 205 Issue: 3 Pages: 822-829

    • DOI

      10.4049/jimmunol.1901008

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The anti-inflammatory effect of the gut lactic acid bacteria-generated metabolite 10-oxo-cis-6,trans-11-octadecadienoic acid on monocytes2020

    • Author(s)
      Hagiwara Shuhei、Nagata Kazuki、Kasakura Kazumi、Sakata Fumiya、Kishino Shigenobu、Ogawa Jun、Yashiro Takuya、Nishiyama Chiharu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 530 Issue: 1 Pages: 342-347

    • DOI

      10.1016/j.bbrc.2020.07.006

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pterostilbene reduces colonic inflammation by suppressing dendritic cell activation and promoting regulatory T cell development2020

    • Author(s)
      Yashiro Takuya、Yura Shiori、Tobita Akari、Toyoda Yuki、Kasakura Kazumi、Nishiyama Chiharu
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 11 Pages: 14810-14819

    • DOI

      10.1096/fj.202001502r

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] シソの葉香気成分の免疫調節作用2020

    • Author(s)
      八代拓也、岡田光、西山千春
    • Journal Title

      AROMA RESEARCH

      Volume: 83 Pages: 242-244

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cooperative Regulation of the Mucosal Mast Cell-Specific Protease Genes Mcpt1 and Mcpt2 by GATA and Smad Transcription Factors.2020

    • Author(s)
      Kasakura K, Nagata K, Miura R, Iida M, Nakaya H, Okada H, Arai T, Arai T, Kawakami Y, Kawakami T, Yashiro T, Nishiyama C.
    • Journal Title

      The Journal of Immunology

      Volume: 204 Issue: 6 Pages: 1641-1649

    • DOI

      10.4049/jimmunol.1900094

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppressive role of PPARγ in the IgE-dependent activation of mast cells.2020

    • Author(s)
      Nagata K, Kasakura K, Miura R, Yashiro T, Nishiyama C.
    • Journal Title

      International Immunology

      Volume: 32 Issue: 2 Pages: 143-150

    • DOI

      10.1093/intimm/dxz069

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PU.1 plays a pivotal role in dendritic cell migration from the periphery to secondary lymphoid organs via regulating CCR7 expression.2019

    • Author(s)
      Yashiro T, Takeuchi H, Nakamura S, Tanabe A, Hara M, Uchida K, Okumura K, Kasakura K, Nishiyama C.
    • Journal Title

      The FASEB Journal

      Volume: 33 Issue: 10 Pages: 11481-11491

    • DOI

      10.1096/fj.201900379rr

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunosuppressive effect of a non-proteinogenic amino acid from Srreptomyces through inhibiting allogeneic T cell proliferation.2019

    • Author(s)
      Yashiro T, Sakata F, Sekimoto T, Shirai T, Hasebe F, Matsuda K, Kurosawa S, Suzuki S, Nagata K, Kasakura K, Nishiyama M, Nishiyama C
    • Journal Title

      Biscience, Biotechnology, and Biochemistry

      Volume: 83 Issue: 6 Pages: 1111-1116

    • DOI

      10.1080/09168451.2019.1591262

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] γ-リノレン酸の乳酸菌代謝物であるγKetoCはNRF2活性化を介して 免疫抑制作用を発揮する2021

    • Author(s)
      八代 拓也、山本 愛日、飯田 真由、大村 さくら、市原 学、 岸野 重信、小川 順、西山 千春
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Research-status Report
  • [Presentation] γ-リノレン酸の乳酸菌代謝産物であるγKetoCは免疫抑制作用を有し皮膚炎を抑制する2020

    • Author(s)
      八代拓也、山本愛日、飯田真由、大村さくら、岸野重信、小川順、西山千春
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 不飽和脂肪酸乳酸菌代謝物の免疫抑制機序の解析2019

    • Author(s)
      飯田真由、八代拓也、小川順、西山千春
    • Organizer
      第15回日本食品免疫学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Pterostilbene exerts immunosuppressive effects through T cells and dendritic cells2019

    • Author(s)
      Takuya Yashiro, Shiori Yura, Akari Tobita, Yuki Toyoda, Chiharu Nishiyama
    • Organizer
      The 7th International Conference on Food Factors
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] NR4A3 plays a critical role in the induction of adaptive immunity via the DC migration from the periphery to second lymphoid organs.2019

    • Author(s)
      Takuya Yashiro, Shiori Nakano, Akihiko Yoshimura, Chiharu Nishiyama
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-12-25  

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