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Regulation of humoral and cellular immune responses by innate immune receptor Gyc76C in Drosophila

Research Project

Project/Area Number 19H03365
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionTohoku University

Principal Investigator

Kurata Shoichiro  東北大学, 薬学研究科, 教授 (90221944)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords自然免疫 / ショウジョウバエ / 液性応答 / 細胞性応答 / cGMP経路 / 液性免疫応答 / 細胞性免疫応答 / NF-κB経路 / NF-κB 経路
Outline of Research at the Start

近年自然免疫系が、病原体成分だけでなく、自己由来のリガンド(内因性リガンド)も認識し、慢性炎症疾患、生活習慣病などの発症に深く関わることが明らかとなってきた。その際、病原体成分では強い反応が一過的に誘導されるのに対して、内因性リガンドでは弱い反応が持続的に誘導され、慢性炎症となる。したがって、これらの疾患発症の理解と、それを標的とした創薬を考える際には、このような自然免疫応答の違いが、どのようにして生じるのかを理解することが重要である。本研究では、ショウジョウバエを用いてこの問題に迫る。

Outline of Final Research Achievements

Innate immunity is involved in chronic inflammatory diseases, cancer metastasis, and lifestyle diseases by recognition of self-ligands. Therefore, understanding of regulation mechanisms of innate immune system is indispensable for understanding of these diseases and drug discovery. We have identified novel cGMP signaling pathway that modulates NF-κB pathway in innate immunity. In this study, we have identified a novel receptor, Gyc76C, which regulates innate immunity. In this study, we have elucidated one aspect of the molecular mechanism by which Gyc76C regulates humoral and cellular immunity.

Academic Significance and Societal Importance of the Research Achievements

自然免疫系が、当初その関連が予想もされなかった、慢性炎症疾患や、ガン転移、生活習慣病などと深い関わりがあることが明らかとなってきた。病原体成分では強い反応が一過的に誘導されるのに対して、慢性炎症では弱い反応が持続的に誘導される。したがって、それらの疾患の理解や創薬には、自然免疫がどのように調節されているかを理解することが重要である。本研究により、同じ受容体が、液性免疫と細胞性免疫を調節する分子機構が明らかとなり、自然免疫制御機構の理解に重要な進展が見られた。

Report

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

    (34 results)

All 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (12 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Remarks (2 results)

  • [Int'l Joint Research] グラスゴー大学(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Glasgow(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Glasgow(英国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] cGMP signaling pathway that modulates NF-κB activation in innate immune responses2021

    • Author(s)
      Kanoh Hirotaka、Iwashita Shinzo、Kuraishi Takayuki、Goto Akira、Fuse Naoyuki、Oshima Yoshiteru、Aigaki Toshiro、Dow Julian A.T.、Davies Shireen-Anne、Kurata Shoichiro(他14名)
    • Journal Title

      iScience

      Volume: 24 Issue: 12 Pages: 103473-103473

    • DOI

      10.1016/j.isci.2021.103473

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Homeostatic Regulation of ROS-Triggered Hippo-Yki Pathway via Autophagic Clearance of Ref(2)P/p62 in the Drosophila Intestine2021

    • Author(s)
      Hiroki Nagai, Hiroshi Tatara, Kyoko Tanaka-Furuhashi, Shoichiro Kurata, Tamaki Yano
    • Journal Title

      Developmental Cell

      Volume: 56 Issue: 1 Pages: 81-94

    • DOI

      10.1016/j.devcel.2020.12.007

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae2021

    • Author(s)
      Raya Tonetti Fernanda、Tomokiyo Mikado、Ortiz Moyano Ramiro、Quilodran-Vega Sandra、Yamamuro Hikari、Kanmani Paulraj、Melnikov Vyacheslav、Kurata Shoichiro、Kitazawa Haruki、Villena Julio
    • Journal Title

      Microorganisms

      Volume: 9:1324 Issue: 6 Pages: 1-19

    • DOI

      10.3390/microorganisms9061324

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ligilactobacillus salivarius Strains Isolated From the Porcine Gut Modulate Innate Immune Responses in Epithelial Cells and Improve Protection Against Intestinal Viral-Bacterial Superinfection2021

    • Author(s)
      Yuhki Indo, Shugo Kitahara, Mikado Tomokiyo, Shota Araki, Md Aminul Islam, Binghui Zhou, Leonardo Albarracin, Ayako Miyazaki, Wakako Ikeda-Ohtsubo, Tomonori Nochi, Takato Takenouchi, Hirohide Uenishi, Hisashi Aso, Hideki Takahashi, Shoichiro Kurata, Julio Villena, Haruki Kitazawa
    • Journal Title

      Front Immunol

      Volume: 12 Pages: 652923-652923

    • DOI

      10.3389/fimmu.2021.652923

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunoglobulin superfamily beat‐Ib mediates intestinal regeneration induced by reactive oxygen species in Drosophila2020

    • Author(s)
      Nagai Hiroki、Kurata Shoichiro、Yano Tamaki
    • Journal Title

      Genes to Cells

      Volume: 25 Issue: 5 Pages: 343-349

    • DOI

      10.1111/gtc.12762

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Ability of Respiratory Commensal Bacteria to Beneficially Modulate the Lung Innate Immune Response Is a Strain Dependent Characteristic2020

    • Author(s)
      Ortiz Moyano Ramiro、Raya Tonetti Fernanda、Tomokiyo Mikado、Kanmani Paulraj、Vizoso-Pinto Maria Guadalupe、Kim Hojun、Quilodr?n-Vega Sandra、Melnikov Vyacheslav、Alvarez Susana、Takahashi Hideki、Kurata Shoichiro、Kitazawa Haruki、Villena Julio
    • Journal Title

      Microorganisms

      Volume: 8 Issue: 5 Pages: 727-727

    • DOI

      10.3390/microorganisms8050727

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of the Immunomodulatory Ability of Lactic Acid Bacteria Isolated from Feedlot Cattle Against Mastitis Using a Bovine Mammary Epithelial Cells In Vitro Assay2020

    • Author(s)
      Fukuyama Kohtaro、Islam Md. Aminul、Takagi Michihiro、Ikeda-Ohtsubo Wakako、Kurata Shoichiro、Aso Hisashi、Vignolo Graciela、Villena Julio、Kitazawa Haruki
    • Journal Title

      Pathogens

      Volume: 9 Issue: 5 Pages: 410-410

    • DOI

      10.3390/pathogens9050410

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Role of Alveolar Macrophages in the Improved Protection against Respiratory Syncytial Virus and Pneumococcal Superinfection Induced by the Peptidoglycan of Lactobacillus rhamnosus CRL15052020

    • Author(s)
      Clua Patricia、Tomokiyo Mikado、Raya Tonetti Fernanda、Islam Md. Aminul、Garc?a Castillo Valeria、Marcial Guillermo、Salva Susana、Alvarez Susana、Takahashi Hideki、Kurata Shoichiro、Kitazawa Haruki、Villena Julio
    • Journal Title

      Cells

      Volume: 9 Issue: 7 Pages: 1653-1653

    • DOI

      10.3390/cells9071653

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Selection of Immunobiotic Ligilactobacillus salivarius Strains from the Intestinal Tract of Wakame-Fed Pigs: Functional and Genomic Studies2020

    • Author(s)
      Binghui Zhou, Leonardo Albarracin, Yuhki Indo, Lorena Arce, Yuki Masumizu, Mikado Tomokiyo, Md. Aminul Islam, Valeria Garcia-Castillo, Wakako Ikeda-Ohtsubo, Tomonori Nochi, Hidetoshi Morita, Hideki Takahashi, Shoichiro Kurata, Julio Villena, Haruki Kitazawa
    • Journal Title

      Microorganisms

      Volume: 8 Issue: 11 Pages: 1659-1659

    • DOI

      10.3390/microorganisms8111659

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A receptor guanylate cyclase, Gyc76C, mediates humoral and cellular responses in distinct ways in Drosophila immunity.2020

    • Author(s)
      Shinzo Iwashita, Hiroaki Suzuki, Akira Goto, Tomohito Oyama, Hirotaka Kanoh, Takayuki Kuraishi, Naoyuki Fuse, Tamaki Yano, Yoshiteru Oshima, Julian A. T. Dow, Shireen-Anne Davies, Shoichiro Kurata
    • Journal Title

      Front. Immunol.

      Volume: 11 Pages: 35-35

    • DOI

      10.3389/fimmu.2020.00035

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HSP70/DNAJA3 chaperone/cochaperone regulates NF-κB activity in immune responses.2019

    • Author(s)
      Kohei Kumada, Naoyuki Fuse, Tomomichi Tamura, Chisaki Okamori, Shoichiro Kurata
    • Journal Title

      Biochemical and Biophysical Research Communications.

      Volume: 513 Issue: 4 Pages: 947-951

    • DOI

      10.1016/j.bbrc.2019.04.077

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual comprehensive approach to decipher the Drosophila Toll pathway, ex vivo RNAi screenings and immunoprecipitation-mass spectrometry.2019

    • Author(s)
      Kanoh H, Kato H, Suda Y, Hori A, Kurata S, Kuraishi T.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 508 Issue: 1 Pages: 332-337

    • DOI

      10.1016/j.bbrc.2018.11.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Neural control of gut homeostasis in Drosophila2021

    • Author(s)
      Shoichiro Kurata
    • Organizer
      The Uehara Memorial Foundation Symposium 2021 “Brain-periphery interactions in health and diseases
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 昆虫の自然免疫2021

    • Author(s)
      倉田祥一朗
    • Organizer
      第120回日本皮膚科学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 腸管損傷応答におけるImmunoglobulin-like domain因子群の機能解析2021

    • Author(s)
      須藤結衣, 倉田祥一朗, 矢野環
    • Organizer
      日本生化学会東北支部 第87回例会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 細胞間接着制御による腸管恒常性維持機構の解析2021

    • Author(s)
      小原 朋子, 倉田 祥一朗, 矢野 環
    • Organizer
      日本生化学会東北支部 第87回例会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 腸管上皮損傷応答におけるImmunoglobulin superfamily因子turtleの機能解析2021

    • Author(s)
      須藤結衣、倉田祥一朗、矢野環
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ショウジョウバエ神経系による腸内細菌叢の制御を介した腸管恒常性維持機構の解析2021

    • Author(s)
      橋場春佳, 石橋謙太朗, 鈴木拓朗, 布施直之, 大坪和香子,北澤春樹,倉田祥一朗
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ショウジョウバエを用いた自然免疫の記憶のゲノム科学解析2021

    • Author(s)
      唐 暢, 岡森千咲, 倉田祥一朗, 布施直之
    • Organizer
      日本比較免疫学会第32回学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Genome-based study of innate immune memory in Drosophila2021

    • Author(s)
      Chang Tang, Chisaki Okamori, Kikuko Hirai, Shoichiro Kurata, Naoyuki Fuse
    • Organizer
      JDRC 14
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コシャペロンDroj2/DNAJA3 による自然免疫シグナル制御2021

    • Author(s)
      熊田幸平、倉田祥一朗
    • Organizer
      第3回 医薬品開発研究センターシンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 自然免疫NF-κB活性化を調節する新規cGMP経路2020

    • Author(s)
      倉田祥一朗
    • Organizer
      第31回日本生体防御学会学術総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 腸管損傷応答におけるロイシンリッチリピート因子tartan、capriciousの機能解析2020

    • Author(s)
      高山倖輔、倉田祥一朗、矢野環
    • Organizer
      第19回 次世代を担う若手ファーマ・バイオフォーラム2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] Genome-based study of innate immune memory in Drosophila2020

    • Author(s)
      Chang Tang, Chisaki Okamori, Kikuko Hirai, Shoichiro Kurata, Naoyuki Fuse
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 自然免疫応答におけるSpatzle isoformの役割2019

    • Author(s)
      二村 麻莉子,上野 春奈,布施 直之,倉田 祥一朗
    • Organizer
      日本生化学会東北支部第85回例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ショウジョウバエ腸管恒常性維持におけるtartan, capriciousの機能解析2019

    • Author(s)
      高山倖輔、倉田祥一朗、矢野環
    • Organizer
      日本生化学会東北支部第85回例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腸管上皮において活性酸素種が与える損傷の受容機構解析2019

    • Author(s)
      高山倖輔、倉田祥一朗、矢野環
    • Organizer
      第58回日本薬学会東北支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ショウジョウバエ腸管損傷応答におけるtartan、capriciousの機能解析2019

    • Author(s)
      高山倖輔、長井広樹、倉田祥一朗、矢野環
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 自然免疫応答におけるSpatzle isoformの役割2019

    • Author(s)
      二村麻莉子,上野春奈,布施直之,倉田祥一朗
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Remarks] 東北大学大学院薬学研究科生命機能解析学分野

    • URL

      http://www.pharm.tohoku.ac.jp/~seimei/seimei_original.html

    • Related Report
      2021 Annual Research Report 2019 Annual Research Report
  • [Remarks] 東北大学大学院薬学研究科生命機能解析学分野

    • URL

      http://www.pharm.tohoku.ac.jp/%7Eseimei/seimei_original.html

    • Related Report
      2020 Annual Research Report

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

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