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Understanding the mechanisms of IRF5-selective regulation towards the development of novel SLE treatment

Research Project

Project/Area Number 16K19161
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionYokohama City University

Principal Investigator

Ban Tatsuma  横浜市立大学, 医学部, 助教 (50635357)

Research Collaborator TAMURA Tomohiko  
NISHIYAMA Akira  
SATO Go  
KIKUCHI Masako  
MANABE Akio  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords転写因子 / IRF5 / 自然免疫応答 / 全身性エリテマトーデス / MAPキナーゼ / 自己免疫疾患 / 全身性エリテマトーデス (SLE) / 免疫学
Outline of Final Research Achievements

In this study, aiming to identify novel therapeutic targets for systemic lupus erythematosus (SLE), a refractory autoimmune disease, we analyzed the selective regulatory mechanism of the transcription factor IRF5, which is involved in the pathogenesis of SLE. As a result, it was suggested that transcription factors activated via the MAP kinase (MAPK) pathway are involved in selective control of IRF5 activity. Furthermore, inhibition of MAPK resulted in suppression of IRF5-dependent innate immune responses in mice. Clarifying the mechanism of IRF5 regulation by transcription factors activated via the MAPK pathway might lead to the development of therapy for SLE and other IRF5-related diseases.

Academic Significance and Societal Importance of the Research Achievements

これまで不明であったMAPキナーゼ経路による選択的なIRF5活性制御機構が存在することを明らかにした。IRF5はSLEのみならず、シェーグレン症候群や全身性強皮症など他の自己免疫疾患の病態発症とも関連するため、IRF5選択的制御機構の解明はこれらの疾患の治療法開発にも繋がると期待できる。

Report

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

    (17 results)

All 2018 2017 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 4 results) Remarks (1 results)

  • [Journal Article] Regulation and role of the transcription factor IRF5 in innate immune responses and systemic lupus erythematosus2018

    • Author(s)
      Ban T, Sato GR, Tamura T
    • Journal Title

      Int Immunol

      Volume: 30 Issue: 11 Pages: 529-536

    • DOI

      10.1093/intimm/dxy032

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 全身性エリテマトーデスの治療法開発に向けた自然免疫応答制御機構の解明2018

    • Author(s)
      藩 龍馬
    • Journal Title

      横浜医学

      Volume: 69 Pages: 59-65

    • Related Report
      2018 Annual Research Report
  • [Journal Article] TLR-MyD88経路と全身性エリテマトーデスにおける転写因子IRF5の制御と役割2018

    • Author(s)
      藩 龍馬, 田村智彦
    • Journal Title

      医学のあゆみ

      Volume: 265 Pages: 1185-1191

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Phos-tag Immunoblot Analysis for Detecting IRF5 Phosphorylation2017

    • Author(s)
      Sato GR, Ban T, Tamura T
    • Journal Title

      Bio-protocol

      Volume: 7 Issue: 10

    • DOI

      10.21769/bioprotoc.2295

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 転写因子IRF5の活性を選択的に阻害する分子Lynの同定と全身性エリテマトーデス2017

    • Author(s)
      藩 龍馬, 田村智彦
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 67 Pages: 532-538

    • NAID

      40021211284

    • Related Report
      2017 Research-status Report
  • [Journal Article] Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity.2016

    • Author(s)
      Ban T., Sato G.R., Nishiyama A., Akiyama A., Takasuna M., Umehara M., Suzuki S., Ichino M., Matsunaga S., Kimura A., Kimura Y., Yanai H., Miyashita S., Kuromitsu J., Tsukahara K., Yoshimatsu K., Endo I., Yamamoto T., Hirano H., Ryo A., Taniguchi T., Tamura T.
    • Journal Title

      Immunity

      Volume: 45 Issue: 2 Pages: 319-332

    • DOI

      10.1016/j.immuni.2016.07.015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] LynはToll様受容体-MyD88シグナル伝達経路において転写因子IRF5を抑制することにより自己免疫疾患の発症を阻止する2016

    • Author(s)
      藩 龍馬, 田村智彦
    • Journal Title

      First Author's

      Volume: - Pages: 089

    • DOI

      10.7875/first.author.2016.089

    • Related Report
      2016 Research-status Report
    • Open Access
  • [Presentation] IRF5 as a potent target beyond type I interferons for the next stage SLE therapy2018

    • Author(s)
      Kikuchi M, Ban T, Sato GR, Manabe A, Yoshimi R, Yanai H, Taniguchi T, Ito S, Tamura T
    • Organizer
      第2回東京理科大-横浜市大合同シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Stepwise and mutual activation of enhancers and promoters during cell differentiation2018

    • Author(s)
      Nishiyama A, Ban T, Fushimi K, Nakabayashi J, Kurotaki D, Tamura T
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] IRF5 as a potent target beyond type I interferons for the next stage SLE therapy2018

    • Author(s)
      Kikuchi M, Ban T, Sato GR, Manabe A, Yoshimi R, Yanai H, Taniguchi T, Ito S, Tamura T
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] LynはTLR-MyD88経路において転写因子IRF5の活性化を抑制することで自己免疫の発症を阻止する2017

    • Author(s)
      藩 龍馬,佐藤 豪,田村 智彦
    • Organizer
      第13回麒麟塾
    • Related Report
      2017 Research-status Report
  • [Presentation] Selective suppression of IRF5 activity by Lyn in the TLR-MyD88 pathway restrains the development of SLE-like disease2017

    • Author(s)
      Ban T, Sato GR, Nishiyama A, Matsunaga S, Kimura A, Kimura Y, Yanai H, Matsumoto Y, Hihara H, Yamamoto T, Hirano H, Ryo A, Tsukahara K, Yoshimatsu K, Taniguchi T, Tamura T
    • Organizer
      Cytokines 2017 (5th Annual Meeting of the International Cytokine & Interferon Society)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] IRF5 hyperactivation caused by Lyn deficiency is linked to the development of SLE-like disease2016

    • Author(s)
      Ban T, Sato GR, Nishiyama A, Ichino M, Yanai H, Ryo A, Taniguchi T, Tamura 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・ラグナガーデンホテル(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Lyn suppresses IRF5 by preventing the stepwise IRF5 post-translational modifications2016

    • Author(s)
      Sato GR, Ban T, Nishiyama A, Ichino M, Yanai H, Ryo A, Taniguchi T, Tamura 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・ラグナガーデンホテル(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 免疫系転写因子IRF5による転写活性化の新規調節機構とその破綻による自己免疫疾患の発症2016

    • Author(s)
      佐藤 豪, 藩 龍馬, 西山 晃, 田村智彦
    • Organizer
      新学術領域研究「転写サイクル」班会議
    • Place of Presentation
      松島一の坊(宮城県宮城郡松島町)
    • Year and Date
      2016-09-05
    • Related Report
      2016 Research-status Report
  • [Presentation] A critical link between Lyn-mediated suppression of the TLR-MyD88-IRF5 pathway and the development of SLE-like disease2016

    • Author(s)
      Ban T, Sato GR, Nishiyama A, Akiyama A, Takasuna M, Umehara M, Suzuki S, Ichino M, Matsunaga S, Kimura A, Kimura Y, Yanai H, Miyashita S, Kuromitsu J, Tsukahara K, Yoshimatsu K, Endo I, Yamamoto T, Hirano H, Ryo A, Taniguchi T, Tamura T
    • Organizer
      The Annual Meeting of the American Association of Immunologists 2016
    • Place of Presentation
      Seattle (USA)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 自然免疫の過剰な反応を防ぐ新たなしくみを発見し、その破綻と自己免疫疾患の関わりを解明!

    • URL

      http://www.yokohama-cu.ac.jp/amedrc/res/tamura_201608.html

    • Related Report
      2016 Research-status Report

URL: 

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

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