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Analysis on molecular mechanisms of antiviral innate immune regulation via RNA sensors

Research Project

Project/Area Number 26293107
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Immunology
Research InstitutionNara Institute of Science and Technology

Principal Investigator

Kawai Taro  奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (50456935)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords自然免疫 / ウイルス感染 / シグナル伝達 / サイトカイン / 免疫学
Outline of Final Research Achievements

Virus infection is usually sensed by innate immune receptors for foreign RNAs such as RIG-I-like receptors (RLRs). In this research, we have identified Arl5b as a negative regulator for RLRs signaling. Moreover, we have discovered a lipid kinase PIKfyve as a positive regulator for RLRs. Moreover, we have identified RNA-binding protein HuR as a positive regulator for RLR signaling. We found that HuR binds to mRNA encoding the kinase Plk2 and it plays a critical roles in induction of type I interferon during RLR signaling. These findings demonstrate that HuR-mediated stabilization of Plk2 mRNA regulates antiviral innate immunity.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(34 results)

All 2017 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 5 results,  Open Access: 7 results) Presentation (21 results) (of which Invited: 2 results) Book (2 results)

  • [Journal Article] DNA-Containing Exosomes Derived from Cancer Cells Treated with Topotecan Activate a STING-Dependent Pathway and Reinforce Antitumor Immunity2017

    • Author(s)
      Kitai Y, Kawasaki T, Sueyoshi T, Kobiyama K, Ishii KJ, Zou J, Akira S, Matsuda T, Kawai T.
    • Journal Title

      J Immunology

      Volume: 198 Pages: 1649-1659

    • DOI

      10.4049/jimmunol.1601694

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response.2017

    • Author(s)
      Kozaki T, Komano J, Kanbayashi D, Takahama M, Misawa T, Satoh T, Takeuchi O, Kawai T, Shimizu S, Matsuura Y, Akira S, Saitoh T
    • Journal Title

      PNAS

      Volume: 114 Pages: 96-101

    • DOI

      10.1073/pnas.1621508114

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cytosolic nucleic acid sensors and innate immune regulation.2017

    • Author(s)
      Ori D, Murase M, Kawai T.
    • Journal Title

      Int Rev Immunol.

      Volume: 36 Pages: 74-88

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IPS-1 differentially induces TRAIL, BCL2, BIRC3 and PRKCE in type I interferons-dependent and -independent anticancer activity.2015

    • Author(s)
      Kumar S, Ingle H, Mishra S, Mahla RS, Kumar A, Kawai T, Akira S, Takaoka A, Raut AA, Kumar H.
    • Journal Title

      Cell Death Dis.

      Volume: 6

    • DOI

      10.1038/cddis.2015.122

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TLR9 signaling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus2015

    • Author(s)
      Matsuda T., Murao N., Katano Y., Juliandi B., Kohyama J., Akira S., Kawai T. & Nakashima K
    • Journal Title

      Nature communications

      Volume: 6 Pages: 1-10

    • DOI

      10.1038/ncomms7514

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Negative regulation of melanoma differentiation-associated gene 5 (MDA5)-dependent antiviral innate immune responses by Arf-like protein 5B.2015

    • Author(s)
      Kitai Y, Takeuchi O, Kawasaki T, Ori D, Sueyoshi T, Murase M, Akira S, Kawai T.
    • Journal Title

      J Biol Chem.

      Volume: 290 Pages: 1269-1280

    • DOI

      10.1074/jbc.m114.611053

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] RIG-I detects mRNA of intracellular Salmonella enterica serovar Typhimurium during bacterial infection.2014

    • Author(s)
      Schmolke M, Patel JR, de Castro E, Sánchez-Aparicio MT, Uccellini MB, Miller JC, Manicassamy B, Satoh T, Kawai T, Akira S, Merad M, García-Sastre A.
    • Journal Title

      MBio.

      Volume: 5

    • DOI

      10.1128/mbio.01006-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pivotal role of RNA-binding E3 ubiquitin ligase MEX3C in RIG-I-mediated antiviral innate immunity.2014

    • Author(s)
      Kuniyoshi K, Takeuchi O, Pandey S, Satoh T, Iwasaki H, Akira S, Kawai T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 111 Pages: 5646-51

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nucleic acid sensing by T cells initiates Th2 cell differentiation.2014

    • Author(s)
      Imanishi T, Ishihara C, Badr Mel S, Hashimoto-Tane A, Kimura Y, Kawai T, Takeuchi O, Ishii KJ, Taniguchi S, Noda T, Hirano H, Brombacher F, Barber GN, Akira S, Saito T
    • Journal Title

      Nat Commun.

      Volume: 10 Pages: 3566-3566

    • DOI

      10.1038/ncomms4566

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Toll-like receptor signaling pathways.2014

    • Author(s)
      Kawasaki T, Kawai T.
    • Journal Title

      Front Immunol.

      Volume: 5 Pages: 461-461

    • DOI

      10.3389/fimmu.2014.00461

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microbial sensing by toll-like receptors and intracellular nucleic acid sensors.2014

    • Author(s)
      Pandey S, Kawai T, Akira S.
    • Journal Title

      Cold Spring Harb Perspect Biol.

      Volume: 7

    • DOI

      10.1101/cshperspect.a016246

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Recognition of PAMPs and DAMPs by mammalian innate immunity2017

    • Author(s)
      Kawai T
    • Organizer
      第58回日本植物生理学会年会
    • Place of Presentation
      鹿児島大学(鹿児島県鹿児島市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Functional elucidation of lipid phosphatases, myotubularin related protein (MTMR) 3 and 4, in modulating antiviral innate immune response2016

    • Author(s)
      Putri DD, Kawasaki T, Kawai T
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Regulation of antiviral innate immunity by an RNA-binding protein HuR2016

    • Author(s)
      Sueyoshi T, Kawasaki T, Kawai T
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Role of endosomal acidification in TLR-mediated inflammatory responses2016

    • Author(s)
      Murase T, Hakozaki R, Kawasaki T, Kawai T
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] PIKfyve regulates development and function of alveolar macrophage2016

    • Author(s)
      Kawasaki T, Kawai T
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肥満誘導に関連した炎症誘導性マクロファージにおけるPIKfyveの役割2016

    • Author(s)
      佐竹茉以、川﨑拓実、河合太郎
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] The role of RNA binding protein Hu antigen R (HuR) in antiviral innate immune responses2016

    • Author(s)
      Sueyoshi T, Kawasaki T, Kawai T
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Toll-Like Receptor (TLR)を介した自然免疫応答におけるV型ATPaseの役割2016

    • Author(s)
      村瀬本弥、箱崎理花、川崎拓実、河合太郎
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] An Endoplasmic reticulum stress transducer CREB3 regulates innate immunity upon viral infection2016

    • Author(s)
      Zobaer H, Monwan W, Kawai T
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Molecular mechanism of IL-33 production2016

    • Author(s)
      Nagayama M, Kawasaki T, Kawai T
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Identification of HuR as a molecule that mediates antiviral innate immune responses2016

    • Author(s)
      Sueyoshi T, Kawasaki T, Kawai T
    • Organizer
      CSHL Meeting: Gene Expression & Signaling in the Immune System
    • Place of Presentation
      Cold Spring Harbor研究所(アメリカ合衆国ニューヨーク州)
    • Year and Date
      2016-04-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] ELMO domain-containing protein 2 (ELMOD2)による抗ウイルス自然免疫制御機構の解析2015

    • Author(s)
      村瀬 本弥、川崎 拓実、河合 太郎
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会合同大会
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] ウイルスRNAに対する自然免疫応答におけるユビキチンリガーゼMex3cの役割2015

    • Author(s)
      河合 太郎、國吉 佳奈子、竹内 理、審良 静男
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会合同大会
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Identification of HuR as a molecule that mediates antiviral innate immune responses2015

    • Author(s)
      Takuya Sueyoshi, Takumi Kawasaki, Taro Kawai
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Role of the lipid kinase PIKfyve in alveolar macrophage2015

    • Author(s)
      Takumi Kawasaki, Taro Kawai
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Identification of HuR as a molecule that mediates antiviral innate immune responses2014

    • Author(s)
      Sueyoshi T, Murase M, Murata R, Kawasaki T, Kawai T.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Physiological role of the lipid kinase PIKfyve in innate immune responses2014

    • Author(s)
      Kawasaki T, Tanaka R, Ito K, Akira S, Kawai T.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Negative regulation of Mda5-mediated antiviral response by Arl5B2014

    • Author(s)
      Kitai Y, Ori D, Sueyoshi T, Murase M, Kawasaki T, Kawai T
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Arl5B-mediated negative regulation of MDA5-dependent innate immune signaling2014

    • Author(s)
      鍛代悠一、織大祐、末吉拓也、村瀬本弥、川崎拓実、竹内理、審良静男、河合太郎
    • Organizer
      第13回あわじしま感染症・免疫フォーラム
    • Place of Presentation
      奈良県新公会堂(奈良県奈良市)
    • Year and Date
      2014-09-23 – 2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Arl5B negatively regulates Mda5-mediated innate immune signaling2014

    • Author(s)
      鍛代悠一、織大輔、末吉拓也、村瀬元弥、川崎拓実、竹内理、審良静男、河合太郎
    • Organizer
      第66回日本細胞生物学会大会
    • Place of Presentation
      奈良県新公会堂(奈良県奈良市)
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 免疫応答におけるホスファチジルイノシトール5リン酸の役割2014

    • Author(s)
      川崎拓実、武村直紀、ダロンスタンドリー、審良静男、河合太郎
    • Organizer
      第66回日本細胞生物学会大会
    • Place of Presentation
      奈良県新公会堂(奈良県奈良市)
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Annual Research Report
  • [Book] 最新醫學増刊号 慢性炎症性疾患の新たな展開2016

    • Author(s)
      村瀬元弥、末吉拓也、河合太郎
    • Total Pages
      9
    • Publisher
      最新医学社
    • Related Report
      2016 Annual Research Report
  • [Book] 臨床免疫・アレルギー科2014

    • Author(s)
      末吉拓也、村瀬本弥、河合太郎
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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