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The role of the TRIM family in systemic lupus erythematosus

Research Project

Project/Area Number 18K16157
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionYokohama City University

Principal Investigator

KAMIYAMA Reikou  横浜市立大学, 医学研究科, 客員研究員 (10739527)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords全身性エリテマトーデス / TRIMファミリー / TRIM21 / TRIM21 / interferon signature / I型IFN
Outline of Final Research Achievements

Although TRIM proteins and related molecules are expected to be involved in a complex manner in systemic lupus erythematosus (SLE), the direct relationship between SLE pathogenesis and TRIM proteins remains unclear. In this study, we generated Trim39 knockout mice and analyzed the immunological role of TRIM39. We found that Trim39-/- mice had significantly larger thymus and spleen weights and a significantly higher number of spleen cells compared to wild-type mice. The expression of STAT1 was significantly upregulated in the B cells of Trim39-/- mice compared to wild-type mice, and the expression of IL-1 was significantly upregulated in the blood of Trim39-/- mice compared to wild-type mice. Trim39-/- mice had significantly higher levels of IL-27 and significantly lower levels of IgG1 and IgA in blood. The amount of IgA in feces was also significantly lower and DSS-induced enteritis was more severe in Trim39-/- mice.

Academic Significance and Societal Importance of the Research Achievements

TRIMファミリーは自然免疫と獲得免疫の両方において様々な役割を担っていることを示す様々な基礎的な報告がみられるが,SLEを含め膠原病疾患において病態への関与を示した報告はまだ少ない.本研究ではTRIM39の免疫学的な機能が明らかになった.SLEの病因が不明であることから根本的な治療はまだなく,ステロイドや免疫抑制薬による治療に依存している.今回の研究結果はTRIM39とその関連分子を標的とした全身性自己免疫疾患の新規治療薬の開発につながる可能性がある.

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2021 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (10 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Anti-TRIM21 antibody is associated with aberrant B-cell function and type I interferon production in systemic lupus erythematosus2021

    • Author(s)
      Kunishita Yosuke、Yoshimi Ryusuke、Kamiyama Reikou、Kishimoto Daiga、Komiya Takaaki、Sakurai Natsuki、Sugiyama Yumiko、Takase-Minegishi Kaoru、Kirino Yohei、Nagaoka Shouhei、Nakajima Hideaki
    • Journal Title

      Lupus

      Volume: 30 Issue: 13 Pages: 2054-2065

    • DOI

      10.1177/09612033211042293

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dysfunction of TRIM21 in interferon signature of systemic lupus erythematosus2018

    • Author(s)
      Kamiyama Reikou、Yoshimi Ryusuke、Takeno Mitsuhiro、Iribe Yasuhiro、Tsukahara Toshinori、Kishimoto Daiga、Kunishita Yosuke、Sugiyama Yumiko、Tsuchida Naomi、Nakano Hiroto、Minegishi Kaoru、Tamura Maasa、Asami Yukiko、Kirino Yohei、Ishigatsubo Yoshiaki、Ozato Keiko、Nakajima Hideaki
    • Journal Title

      Modern Rheumatology

      Volume: 28 Issue: 6 Pages: 993-1003

    • DOI

      10.1080/14397595.2018.1436028

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Anti-TRIM21 antibody is associated with type I interferon and B-cell abnormalities in systemic lupus erythematosus.2021

    • Author(s)
      Yosuke Kunishita, Ryusuke Yoshimi, Naoki Suzuki, Yuki Iizuka, Masaki Mitsuhashi, Takaaki Komiya, Natsuki Sakurai, Yumiko Sugiyama, Daiga Kishimoto, Reikou Kamiyama, Yohei Kirino, Shouhei Nagaoka, Hideaki Nakajima
    • Organizer
      第65回日本リウマチ学会総会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The clinical feature of late-onset systemic lupus erythematosus: The LUNA registry study.2019

    • Author(s)
      Natsuki Sakurai, Ryusuke Yoshimi, Chiharu Hidekawa, Masaki Mitsuhashi, Yumiko Sugiyama, Yosuke Kunishita, Daiga Kishimoto, Yuki Iizuka, Takaaki Komiya, Hideto Nagai, Naoki Hamada, Naomi Tsuchida, Yutaro Soejima, Reikou Kamiyama, et al.
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] LUNAレジストリを用いた全身性エリテマトーデスにおけるタクロリムス使用患者の臨床像の検討.2019

    • Author(s)
      三橋正季, 國下洋輔, 吉見竜介, 秀川智春, 櫻井菜月, 杉山裕美子, 岸本大河, 飯塚友紀, 小宮孝章, 永井秀人, 濱田直樹, 土田奈緒美, 副島裕太郎, 神山玲光, 小林幸司, 浅見由希子, 桐野洋平, 矢嶋宣幸, 佐田憲映, 一瀬邦弘, 大野滋, 中島秀明
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Dysfunction of Trim21 promotes aberrant B cell differentiation in systemic lupus erythematosus.2019

    • Author(s)
      Yosuke Kunishita, Ryusuke Yoshimi, Reikou Kamiyama, Daiga Kishimoto, Takaaki Komiya, Yumiko Sugiyama, Yohei Kirino, Hideaki Nakajima
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 全身性エリテマトーデスにおいてLLDAS達成に影響を与える因子の探索- LUNAレジストリを用いた横断研究.2019

    • Author(s)
      岸本大河, 吉見竜介, 國下洋輔, 秀川智春, 櫻井菜月, 三橋正季, 杉山裕美子, 飯塚友紀, 小宮孝章, 永井秀人, 濱田 直樹, 土田奈緒 美, 副島裕太郎, 神山玲光, 小林幸司, 浅見由希子, 桐野洋平, 矢嶋宣幸, 佐田憲映, 一瀬邦弘, 大野滋, 中島秀明
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 全身性エリテマトーデスにおけるヒドロキシクロロキン使用患者の臨床像について ― LUNAレジストリを用いた横断研究.2019

    • Author(s)
      杉山裕美子, 吉見竜介, 國下洋輔, 秀川智春, 櫻井菜月, 三橋正季, 岸本大河, 飯塚友紀, 小宮孝章, 永井秀人, 濱田直樹, 土田奈緒美, 副島裕太郎, 神山玲光, 小林幸司, 浅見由希子, 桐野洋平, 矢嶋宣幸, 佐田憲映, 一瀬邦弘, 大野 滋, 中島秀明
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 全身性エリテマトーデスにおけるニューモシスチス肺炎予防の現状 - 多施設共同レジストリLUNAより.2019

    • Author(s)
      吉見竜介, 國下洋輔, 秀川智春, 櫻井菜月, 三橋正季, 杉山裕美子, 岸本大河, 飯塚友紀, 小宮孝章, 永井秀人, 濱田直樹, 土田奈緒美, 副島裕太郎, 神山玲光, 小林幸司, 浅見由希子, 桐野洋平, 矢嶋宣幸, 佐田憲映, 一瀬邦弘, 宮本俊明, 大野滋, 中島秀明
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 全身性エリテマトーデスにおける感染症既往の実態について - LUNAレジストリによる横断研究.2019

    • Author(s)
      秀川智春, 國下洋輔, 吉見竜介, 櫻井菜月, 三橋正季, 杉山裕美子, 岸本大河, 飯塚友紀, 小宮孝章, 永井秀人, 濱田直樹, 土田奈緒美, 副島裕太郎, 神山玲光, 小林幸司, 浅見由希子, 桐野洋平, 矢嶋宣幸, 佐田憲映, 一瀬邦弘, 大野滋, 中島秀明
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Dysfunction of TRIM21 promotes aberrant plasmablast differentiation in systemic lupus erythematosus due to the reduction of TRIM21-mediated ubiquitylation of IRF52019

    • Author(s)
      Yosuke Kunishita, Ryusuke Yoshimi, Reikou Kamiyama, Daiga Kishimoto, Koji Yoshida, Eijin Hashimoto, Yumiko Sugiyama, Takaaki Komiya, Natsuki Sakurai, Yohei Kirino, Hideaki Nakajima
    • Organizer
      American College of Rheumatology 83rd Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 全身性エリテマトーデスのB細胞分化異常におけるTRIM21の役割2018

    • Author(s)
      國下洋輔
    • Organizer
      JCRベーシックリサーチカンファレンス
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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