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Regulation of Immune Responses by the transcription regulatior IkappaBzeta and its binding protein

Research Project

Project/Area Number 16K08747
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionToho University

Principal Investigator

YAMAZAKI Soh  東邦大学, 医学部, 准教授 (70315084)

Research Collaborator KATAGIRI Takaharu  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsIkappaBzeta / JunB / Th17 / 自己免疫疾患 / ヘルパーT細胞 / Th17細胞 / 制御性T細胞 / IκBζ / NF-κB / 自然免疫 / マクロファージ / 発現制御 / 免疫学
Outline of Final Research Achievements

Although IL-17-producing T helper (Th17) cells are associated with autoimmune diseases such as multiple sclerosis, development of the cells has not been fully understood. While the transcription factor JunB is known to be involved in barrier function of skin and regulation of myeloid cells, it role in immune cells was not known. We elucidated that Junb-deficient naive CD4+ T cells were incapable of differentiating into Th17 cells, and that mice deficient in JunB are totally resistant to EAE, an animal model for human multiple sclerosis.

Academic Significance and Societal Importance of the Research Achievements

多発性硬化症をはじめ、リウマチ関節炎や乾癬などの自己免疫疾患は治療戦略はもとより、病態の発症メカニズムについても詳細が不明だった。今回の発見に基づき、JunBのはたらきを阻害するというアプローチにより自己免疫疾患を抑えるという新しい治療法の可能性が開けた。

Report

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

    (20 results)

All 2019 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Development of novel methods that monitor necroptosis and the release of DAMPs at the single cell resolution2019

    • Author(s)
      Nakano Hiroyasu、Murai Shin、Yamaguchi Yoshifumi、Shirasaki Yoshitaka、Nakabayashi Osamu、Yamazaki Soh
    • Journal Title

      Cell Stress

      Volume: 3 Issue: 2 Pages: 66-69

    • DOI

      10.15698/cst2019.02.177

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A murine model of acute lung injury identifies growth factors to promote tissue repair and their biomarkers2018

    • Author(s)
      Kurosawa Takeyuki、Miyoshi Shion、Yamazaki Soh、Nishina Takashi、Mikami Tetuo、Oikawa Akira、Homma Sakae、Nakano Hiroyasu
    • Journal Title

      Genes to Cells

      Volume: 24 Issue: 2 Pages: 112-125

    • DOI

      10.1111/gtc.12659

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AP-1転写因子JunBによるTh17細胞分化の制御2018

    • Author(s)
      山﨑 創
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 70 Pages: 275-282

    • Related Report
      2018 Annual Research Report
  • [Journal Article] The AP-1 transcription factor JunB is required for Th17 cell differentiation2017

    • Author(s)
      Yamazaki Soh、Tanaka Yoshihiko、Araki Hiromitsu、Kohda Akira、Sanematsu Fumiyuki、Arasaki Tomoko、Duan Xuefeng、Miura Fumihito、Katagiri Takaharu、Shindo Ryodai、Nakano Hiroyasu、Ito Takashi、Fukui Yoshinori、Endo Shogo、Sumimoto Hideki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 17402-17402

    • DOI

      10.1038/s41598-017-17597-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 肝炎の制御における骨髄由来細胞の役割2017

    • Author(s)
      山崎 創, 朴 雪花, 中野 裕康
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 68 Pages: 455-462

    • Related Report
      2017 Research-status Report
  • [Journal Article] Depletion of myeloid cells exacerbates hepatitis and induces an aberrant increase in histone H3 in mouse serum2017

    • Author(s)
      Piao, X. Yamazaki, S. Komazawa-Sakon, S. Miyake, S. Nakabayashi, O. Kurosawa, T. Mikami, T. Tanaka, M. Van Rooijen, N. Ohmuraya, M. Oikawa, A. Kojima, Y. Kakuta, S. Uchiyama, Y. Tanaka, M. Nakano, H.
    • Journal Title

      Hepatology

      Volume: 65 Issue: 1 Pages: 237-252

    • DOI

      10.1002/hep.28878

    • NAID

      120006528815

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Critical contribution of nuclear factor erythroid 2-related factor 2 (NRF2) to electrophile-induced Interleukin-11 production.2017

    • Author(s)
      Nishina T, Deguchi Y, Miura R, Yamazaki S, Shinkai Y, Kojima Y, Okumura K, Kumagai Y, Nakano H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 1 Pages: 205-216

    • DOI

      10.1074/jbc.m116.744755

    • NAID

      120007135104

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The nuclear protein IκBζ forms a transcriptionally active complex with nuclear factor-κB (NF-κB) p50 and Lcn2 promoter via the N- and C-terminal ankyrin repeat motifs2016

    • Author(s)
      Kohda A, Yamazaki S, Sumimoto H.
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Issue: 39 Pages: 20739-20752

    • DOI

      10.1074/jbc.m116.719302

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Short form FLICE-inhibitory protein promotes TNFalpha-induced necroptosis in fibroblasts derived from CFLARs transgenic mice2016

    • Author(s)
      Shindo, R. Yamazaki, S. Ohmuraya, M. Araki, K. Nakano, H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 480 Issue: 1 Pages: 23-28

    • DOI

      10.1016/j.bbrc.2016.10.015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] A crucial role of JunB in attenuating epithelial damage-induced colitis through induction of regulatory T cells2018

    • Author(s)
      Soh Yamazaki, Takaharu Katagiri, Hideki Sumimoto, Hiroyasu Nakano
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腸管上皮バリアにおける転写因子JunBの役割2018

    • Author(s)
      片桐 翔治, 山﨑 創, 三上 哲夫, 遠藤 昌吾, 住本 英樹, 亀田 秀人, 中野 裕康
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] RIPK3-dependent necroptosis of intestinal epithelial cells results in RORgt+ innate lymphoid cells-dependent lethal ileitis2018

    • Author(s)
      Ryodai Shindo, Masaki Ohmuraya, Sachiko Komazawa-Sakon, Sanae Miyake, Soh Yamazaki, Takashi Nishina, Manolis Pasparakis, Kimi Araki, Hiroyasu Nakano
    • Organizer
      2nd Australia-Japan Meeting on Cell Death
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The AP-1 transcription factor JunB is essential for development of Th17 cells2017

    • Author(s)
      Yamazaki S, Tanaka Y, Fukui Y, Sumimoto H
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] RORgammat-positive cells mediate RIPK3-and MLKL-dependent lethal ileitis in neonatal mice2017

    • Author(s)
      Shindo R, Yamazaki S, Nakano H
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝特異的cFLIP低発現マウスを用いた肝障害モデルの解析2017

    • Author(s)
      山崎 創, 朴 雪花, 駒澤-左近 幸子, 三宅 早苗, 中林 修, 田中 稔, 大村谷 昌樹, 及川 彰, 角田 宗一郎, 内山 安男, 田中 正人, 中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] RORgammat陽性細胞はRIPK3およびMLKL依存性に小腸炎を誘導する2017

    • Author(s)
      進藤 綾大, 大村谷 昌樹, 駒澤 幸子, 三宅 早苗, 山崎 創, 仁科 隆史, 小西 博之, 木山 博資, 三上 哲夫, 荒木 喜美, 中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] II型肺胞上皮細胞の障害と再生に関する解析2017

    • Author(s)
      三好 嗣臣, 黒澤 武介, 仁科 隆史, 山崎 創, 本間 栄, 中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞死制御因子cFLIPの肝細胞特異的欠損マウスを用いた肝障害モデルにおけるクッパー細胞および骨髄由来細胞の役割2016

    • Author(s)
      朴 雪花, 山﨑 創, 駒澤-左近 幸子, 三宅 早苗, 中林 修, 田中 稔, 大村谷 昌樹, 及川 彰, 角田 宗一郎, 内山 安男, 田中 正人, 中野 裕康
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター/東北大学川内北キャンパス (宮城県・仙台市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
  • [Presentation] アポトーシス細胞は腸内細菌非依存的にReg3βを産生し腸管の恒常性を維持する2016

    • Author(s)
      進藤 綾大, 大村谷 昌樹, 駒澤 幸子, 三宅 早苗, 山﨑 創, 仁科 隆史, 小西 博之, 木山 博資, 三上 哲夫, 荒木 喜美, 中野 裕康
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター/東北大学川内北キャンパス (宮城県・仙台市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 転写因子NF-κBとそのパートナータンパク質IκBζによる転写活性化複合体の形成機構2016

    • Author(s)
      神田 朗, 山﨑 創, 住本 英樹
    • Organizer
      第27回日本生体防御学会学術総会
    • Place of Presentation
      九州大学病院キャンパス内コラボステーションⅠ視聴覚ホール (福岡県・福岡市)
    • Year and Date
      2016-07-09
    • Related Report
      2016 Research-status Report

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

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