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Elucidation of the mechanism for regulatory B cell differentiation by nephronectin and establishment of a novel therapeutic strategy for autoimmune diseases

Research Project

Project/Area Number 16K08221
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionFukuyama University

Principal Investigator

KON Shigeyuki  福山大学, 薬学部, 教授 (90344499)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsネフロネクチン / 制御性B細胞 / カルシウム結合 / 自己免疫疾患 / サンドイッチELISAシステム / 細胞外基質 / インテグリン / カルシウム結合タンパク質 / 抗体 / 免疫学 / 薬学
Outline of Final Research Achievements

We found that nehronectin (Npnt), which is a extracellular matrix, is involved in autoimmune diseases, and inhibits regulatory B cell (Breg) differentiation. We also found that Npnt is a calcium-binding protein. It has reported that calcium signaling is important for Breg differentiation. Therefore, we asked whether calcium-binding ability of Npnt is involved in the autoimmune diseases via inhibition of Breg differentiation. To identification of calcium-binding site of Npnt, radioactive isotope of calcium was used. Then, we identified the site in Link region. An antibody against calcium-binding region of Npnt was generated by immunization of the synthetic peptide and injected into experimental autoimmune encephalitis (EAE) model. EAE score examination revealed that there is no difference between anti-calcium-binding region of Npnt antibody and control antibody. These data suggest that calcium-binding ability of Npnt is not involved in the autoimmune diseases.

Academic Significance and Societal Importance of the Research Achievements

免疫抑制機能を有するB細胞である制御性B細胞(Breg)は、自己免疫疾患との関与が推察されているが、その分化メカニズムの多くは不明である。当研究室では、細胞外基質ネフロネクチン(Npnt)研究からNpntがCa結合タンパク質であること、自己免疫疾患増悪化に関与すること、Breg分化を抑制する機能を有することを見出していることから、NpntのCa結合能のBreg分化への関与を予想し、NpntのCa結合領域を同定した。NpntのCa結合領域に対する抗体を作製し、Breg分化や自己免疫疾患抑制効果を検討した結果、NpntのCa結合能はBreg分化には影響与えないことが分かった。

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 Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] The role of α9β1 integrin and its ligands in the development of autoimmune diseases.2018

    • Author(s)
      Kon S, Uede T.
    • Journal Title

      J Cell Commun Signal.

      Volume: 12 Issue: 1 Pages: 333-342

    • DOI

      10.1007/s12079-017-0413-7

    • NAID

      120007018386

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lactobacillus helveticus SBT2171 Attenuates Experimental Autoimmune Encephalomyelitis in Mice.2018

    • Author(s)
      Yamashita M, Ukibe K, Matsubara Y, Hosoya T, Sakai F, Kon S, Arima Y, Murakami M, Nakagawa H, Miyazaki T.
    • Journal Title

      Front Microbiol

      Volume: 8 Pages: 2596-2596

    • DOI

      10.3389/fmicb.2017.02596

    • NAID

      120006414007

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel α9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases.2017

    • Author(s)
      Matsumoto N, Kon S, Nakatsuru T, Miyashita T, Inui K, Saitoh K, Kitai Y, Muromoto R, Kashiwakura JI, Uede T, Matsuda T.
    • Journal Title

      J Immunol.

      Volume: 199 Issue: 1 Pages: 82-90

    • DOI

      10.4049/jimmunol.1601329

    • NAID

      120007007782

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-IL-17A blocking antibody reduces cyclosporinA-induced relapse in experimental autoimmune encephalomyelitis mice2016

    • Author(s)
      Saitoh K, Kon S, Nakatsuru T, Inui K, Ihara T, Matsumoto N, Kitai Y, Muromoto R, Matsuda T
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 8 Pages: 139-45

    • DOI

      10.1016/j.bbrep.2016.08.021

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A new STAT3-binding partner, ARL3, enhances the phosphorylation and nuclear accumulation of STAT3.2016

    • Author(s)
      Togi S, Muromoto R, Hirashima K, Kitai Y, Okayama T, Ikeda O, Matsumoto N, Kon S, Sekine Y, Oritani K, Matsuda T.
    • Journal Title

      J Biol Chem.

      Volume: 印刷中 Issue: 21 Pages: 11161-11171

    • DOI

      10.1074/jbc.m116.724849

    • NAID

      120006219975

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 抗β8インテグリン抗体を用いた四塩化炭素誘導肝線維化モデル抑制効果の検討2018

    • Author(s)
      重政 歩美、本田 真知子、今 重之
    • Organizer
      第57回日本薬学会中国四国支部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新規α4インテグリンスプライシングバリアントの同定とその機能解析2018

    • Author(s)
      川崎 岬、重政 歩美、本田 真知子、今 重之
    • Organizer
      第57回日本薬学会中国四国支部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗オステオポンチン抗体を用いた非アルコール性脂肪肝炎増悪化抑制効果の検討2018

    • Author(s)
      本田 真知子、宮崎 純子、今 重之
    • Organizer
      第57回日本薬学会中国四国支部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新たな反応性を有する抗β8インテグリン抗体を用いた肝線維化モデル抑制効果の検討2018

    • Author(s)
      重政 歩美、本田 真知子、今 重之
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新規α4インテグリンスプライシングバリアントは内在性α4インテグリン機能抑制分子である2018

    • Author(s)
      重政歩美、乾恭輔、本田真知子、松田正、今重之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 自己免疫疾患における細胞外基質ネフロネクチンの関与2018

    • Author(s)
      藤岡和征、本田真知子、松田正、今重之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞外基質ネフロネクチンに対するサンドイッチELISAシステムの構築2018

    • Author(s)
      本田真知子、李 順姫、松田正、大槻剛巳、今重之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] The role of signal-transducing adaptor protein-1 in Concanavalin A-induced hepatitis2018

    • Author(s)
      Takeru Ihara, Kodai Saitoh, Shigeyuki Kon, Junichi Kashiwakura, Ryuta Muromoto, Yuichi Kitai, Tadashi Matsuda
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Soluble alpha4 integrin splicing variant is a novel endogenous integrin inhibitor2016

    • Author(s)
      Kon S, Inui K, Saitoh K, Matsumoto N, Matsuda 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 Research-status Report
  • [Presentation] XCL1/Lymphotactin, a novel ligand of alpha9 integrin, is involved in the development of autoimmune diseases2016

    • Author(s)
      Matsumoto N, Kon S, Nakatsuru T, Matsuda 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 Research-status Report
  • [Presentation] T細胞活性化および免疫応答におけるSTAP-2の機能解析2016

    • Author(s)
      齋藤浩大、今重之、小澤清貴、伊原建、関根勇一、室本竜太、鍛代悠一、吉村昭彦、織谷健司、松田正
    • 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] インテグリを介した細胞接着の機能抑制による自己免疫疾患治療戦略2016

    • Author(s)
      今 重之
    • Organizer
      第135回日本薬学会中国四国支部例会
    • Place of Presentation
      福山大学(広島県、福山市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] 福山大学薬学部分子免疫学研究室ホームページ

    • URL

      http://web.fukuyama-u.ac.jp/pharm/htmls/Labo/labs/mol.immun/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 自己免疫疾患増悪化に関わる新たなα9インテグリンのリガンドXCL1の発見

    • URL

      http://www.fukuyama-u.ac.jp/info/press-release/entry-4336.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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