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Regulation mechanisms of novel cytokine production by metal trace elements

Research Project

Project/Area Number 16K18518
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionKanazawa Medical University

Principal Investigator

YABE-WADA Toshiki  金沢医科大学, 医学部, 講師 (10451634)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsサイトカイン / 自然免疫 / RNA結合蛋白質 / 蛋白質輸送 / 転写後制御 / 膜蛋白質 / 転写後発現制御 / 生体金属イオン / TLR / Toll様受容体
Outline of Final Research Achievements

The regulation of the proinflammatory cytokine production by immune cells is important for the appropriate inflammatory responses. In this study, we focused on the regulation of cytokine secretion in immune cells. We identified Sortilin which is involved in IFN-α secretion in plasmacytoid dendritic cells (pDC), and Sortilin transcripts degraded posttranscriptionally upon stimulation with various TLR ligands. The nucleotide-binding ability of poly-rC-binding proteins, which can act as a trans-acting factor to stabilize Sortilin mRNA, was impaired by zinc ions and alterations of intracellular zinc affect sortilin expression. Poly-rC-binding proteins may posttranscriptionally regulate Sortilin transcripts by sensing intracellular zinc levels.

Academic Significance and Societal Importance of the Research Achievements

免疫細胞から産生される炎症性サイトカインの分泌制御は,適切な炎症応答を保つうえで極めて重要である.本研究では,抗ウイルス免疫に関与する形質細胞様樹状細胞(pDC)において,IFN-α分泌に関わる分子としてSortilinを同定し,その重要性を明らかにした.また,SortilinがTLRシグナル依存的にmRNAレベルで発現制御を受けており,その制御にRNA結合蛋白質であるポリC結合蛋白質が関与している事,更に細胞内の亜鉛がSortilinの制御に関わることを明らかにした.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 5 results) Remarks (1 results)

  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] National Institutes of Health(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Crystal structure of the ligand-free form of the Vps10 ectodomain of dimerized Sortilin at acidic pH.2018

    • Author(s)
      Yabe-Wada T, Matsuba S, Unno M, Onai N.
    • Journal Title

      FEBS Lett.

      Volume: 592 Issue: 15 Pages: 2647-2657

    • DOI

      10.1002/1873-3468.13181

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Secretory Leukoprotease Inhibitor As an Endogenous Negative Regulator in Allergic Effector Cells2017

    • Author(s)
      Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Tetsuya Sato, Mikita Suyama, Toshiyuki Takai, Toshiaki Kikuchi, Toshihiro Nukiwa, Akira Nakamura
    • Journal Title

      Frontiers in Immunology

      Volume: 8 Pages: 1538-1538

    • DOI

      10.3389/fimmu.2017.01538

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monomeric Form of Peptidylarginine Deiminase Type I Revealed by X-ray Crystallography and Small-Angle X-ray Scattering.2016

    • Author(s)
      Saijo, S., Nagai, A., Kinjo, S., Mashimo, R., Akimoto, M., Kizawa, K., Yabe-Wada, T., Shimizu, N., Takahara, H., Unno, M.
    • Journal Title

      J. Mol. Biol.

      Volume: 428 Issue: 15 Pages: 3058-3073

    • DOI

      10.1016/j.jmb.2016.06.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] TLR signals posttranscriptionally regulate the cytokine trafficking mediator sortilin.2016

    • Author(s)
      Yabe-Wada T, Matsuba S, Takeda K, Sato T, Suyama M, Ohkawa Y, Takai T, Shi H, Philpott CC, Nakamura A.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 26566-26566

    • DOI

      10.1038/srep26566

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] サイトカイン輸送に関与するSortilinの転写後発現制御機2018

    • Author(s)
      和田俊樹,松葉慎太郎,小内伸幸
    • Organizer
      第28回日本樹状細胞研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 酸性条件下で2量体化するSortilinの結晶構造2018

    • Author(s)
      和田俊樹,松葉慎太郎,海野昌喜,小内伸幸
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A Glutaredoxin-BolA complex serves as an iron-sulfur cluster chaperone for the cytosolic cluster assembly machinery2017

    • Author(s)
      Avery Frey, Dan Palenchar, Kym Zumbrennen, Toshiki Yabe, Ajay Vashisht, Justin Wildemann, James Wohlschlegel, Caroline Philpott
    • Organizer
      2017 International BioIron Society Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Involvement of poly-rC binding proteins in posttranscriptional regulation of Sortilin, the cytokine trafficking mediator2017

    • Author(s)
      Toshiki Yabe-Wada, Shintaro Matsuba, Kazuya Takeda, Akira Nakamura, Caroline C Philpott, Nobuyuki Onai
    • Organizer
      Cytokines 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ポリC結合蛋白質によるSortilinの転写後発現制御機構2017

    • Author(s)
      和田 俊樹、松葉 慎太郎、小内 伸幸
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Involvement of poly-rC binding proteins in posttranscriptional regulation of Sortilin, the cytokine trafficking mediator2017

    • Author(s)
      Toshiki Yabe-Wada, Shintaro Matsuba, Caroline C. Philpott, Nobuyuki Onai
    • Organizer
      RNAフロンティアミーティング2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Involvement of poly-rC binding proteins in posttranscriptional regulation of sortilin2016

    • Author(s)
      T.Yabe-Wada, S.Matsuba, CC Philpott
    • 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 Research-status Report
  • [Presentation] Structural Studies of Peptidylarginine Deiminase Type I using X-ray Crystallography and Small-Angle X-ray Scattering2016

    • Author(s)
      A.Nagai, S.Saijo, S.Kinjo, R.Mashimo, M.Akimoto, K.Kizawa, T.Yabe-Wada, N.Shimizu, H.Takahara, M.Unno
    • Organizer
      The International Symposium of Quantum Beam Science at Ibaraki University
    • Place of Presentation
      Ibaraki University, Mito, JAPAN
    • Year and Date
      2016-11-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] X線結晶構造解析とX線小角散乱による蛋白質脱イミノ化酵素PAD1の構造2016

    • Author(s)
      永井杏奈,西條慎也,金城沙弥,眞下隆太朗,秋元恵,清水伸隆,高原英成,木澤謙司,和田俊樹,海野昌喜
    • Organizer
      日本結晶学会年会2016
    • Place of Presentation
      茨城県立県民文化センター(茨城県水戸市)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Research-status Report
  • [Presentation] TLR signals posttranscriptionally regulate the cytokine trafficking mediator sortilin2016

    • Author(s)
      T.Yabe-Wada, S.Matsuba, K.Takeda, T.Sato, M.Suyama, Y.Ohkawa, H.Shi, C.C.Philpott, A.Nakamura
    • Organizer
      Gordon Research Conference on Protein Processing, Trafficking and Secretion
    • Place of Presentation
      Colby-Sawyer College in New London NH United States
    • Year and Date
      2016-07-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural Studies of Peptidylarginine Deiminase Type I using X-ray Crystallography and Small-angle X-ray Scattering2016

    • Author(s)
      A.Nagai, S.Saijo, S.Kinjo, R.Mashimo, M.Akimoto, K.Kizawa, T.Yabe-Wada, N.Shimizu, H.Takahara, M.Unno
    • Organizer
      14th International Conference of the Asian Crystallographic Association
    • Place of Presentation
      Hanoi University of Science and Technology, Hanoi, Vietnam
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] -新たなサイトカイン分泌制御機構の発見-自己免疫疾患などに対する新たな治療法の開発への貢献に期待

    • URL

      http://www.kanazawa-med.ac.jp/blog/2016/05/post-425.html?fi=1

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-21  

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