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The role of ILCs in the development of rheumatoid arthritis

Research Project

Project/Area Number 16K09897
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionKyushu University

Principal Investigator

Arinobu Yojiro  九州大学, 大学病院, 講師 (90467928)

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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords関節リウマチ / 自然リンパ球 / Th17サイトカイン / CCR6 / ILC3 / IL-17 / IL-22 / arthritis / IL-17A
Outline of Final Research Achievements

Recent studies show that Innate Lymphoid Cells (ILCs) contribute to development of chronic inflammation and autoimmune disease. In this study, we assessed ILC function in the pathogenesis of rheumatoid arthritis (RA). In the mouse of collagen-induced arthritis (CIA) , the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p=0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p=0.015). In RA patients, relatively high levels of CCR6+ ILC3s in SF were positively correlated with tender joint count (TJC) and swollen joint count (SJC) (ρ=0.689, p=0.0032 and ρ=0.644, p=0.0071 respectively). These data suggest that CCR6+ ILC3s are positively associated with RA development through production of IL-17 and IL-22.

Academic Significance and Societal Importance of the Research Achievements

近年、関節リウマチの治療成績は飛躍的に改善したが、未だ臨床的寛解に到達できず、関節破壊が進行する症例が少なからず存在する。この理由の一つに、未だ解明できていない病態があり、その制御が不十分な可能性がある。今回我々は、新規細胞系列であるILCに着目した。この細胞系列は、ヘルパーT細胞に非常に類似した機能を有している。本研究にて、関節炎発症においてCCR6+ILC3が関与している可能性が新たに示唆された。これにより、関節リウマチの病態の理解が進むだけでなく、関節リウマチの新たな治療戦略構築にも役立つと考えられる。

Report

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

    (18 results)

All 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Are the 2016 EULAR/ACR/PRONTO classification criteria for macrophage activation syndrome applicable to patients with adult-onset Still's disease?2019

    • Author(s)
      Tada Y, Inokuchi S, Maruyama A, Suematsu R, Sakai M, Sadanaga Y, Ono N, Arinobu Y, Koarada S
    • Journal Title

      Rheumatol Int.

      Volume: 39 Issue: 1 Pages: 97-104

    • DOI

      10.1007/s00296-018-4114-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD34-selected versus unmanipulated autologous hematopoietic stem cell transplantation in the treatment of severe systemic sclerosis: a post hoc analysis of a phase I/II clinical trial conducted in Japan.2019

    • Author(s)
      Ayano M, Tsukamoto H, Mitoma H, Kimoto Y, Akahoshi M, Arinobu Y, Miyamoto T, Horiuchi T, Niiro H, Nagafuji K, Harada M, Akashi K
    • Journal Title

      Arthritis Res Ther.

      Volume: 21 Issue: 1 Pages: 30-30

    • DOI

      10.1186/s13075-019-1823-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of tumor necrosis factor inhibitors and tocilizumab on the glycosylated hemoglobin levels in patients with rheumatoid arthritis; an observational study2018

    • Author(s)
      (2)Otsuka Y, Kiyohara C, Kashiwado Y, Sawabe T, Nagano S, Kimoto Y, Ayano M, Mitoma H, Akahoshi M, Arinobu Y, Niiro H, Akashi K, Horiuchi T
    • Journal Title

      PLoS One

      Volume: 13 Issue: 4 Pages: e0196368-e0196368

    • DOI

      10.1371/journal.pone.0196368

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ultrasonographic efficacy of biologic and targeted synthetic DMARDs therapy in RA from multicenter RA ultrasound prospective cohort in Japan2018

    • Author(s)
      Nishino Ayako、Kawashiri Shin-ya、Koga Tomohiro、Iwamoto Naoki、Ichinose Kunihiro、Tamai Mami、Nakamura Hideki、Origuchi Tomoki、Ueki Yukitaka、Yoshitama Tamami、Eiraku Nobutaka、Matsuoka Naoki、Okada Akitomo、Fujikawa Keita、Hamada Hiroaki、Tsuru Tomomi、Nagano Shuji、Arinobu Yojiro、Hidaka Toshihiko、Kawakami Atsushi
    • Journal Title

      Arthritis Care & Research

      Volume: 26 Issue: 12 Pages: 1719-1726

    • DOI

      10.1002/acr.23551

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of unipotent megakaryocyte progenitors in human hematopoiesis.2017

    • Author(s)
      K. Miyawaki. Iwasaki, T. Jiromaru, H. Kusumoto, A. Yurino, T. Sugio, Y. Uehara, J. Odawara, S. Daitoku, Y. Kunisaki, Y. Mori, Y. Arinobu, H. Tsuzuki, Y. Kikushige, T. Iino, K. Kato, K. Takenaka, T. Miyamoto, T. Maeda, *K. Akashi
    • Journal Title

      Blood

      Volume: 印刷中 Issue: 25 Pages: 3332-3343

    • DOI

      10.1182/blood-2016-09-741611

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Notch1 expression is regulated at the post-transcriptional level by the 3′ untranslated region in hematopoietic stem cell development2017

    • Author(s)
      Mizuno Shinichi、Iino Tadafumi、Ozawa Hidetoshi、Arinobu Yojiro、Chong Yong、Akashi Koichi
    • Journal Title

      International Journal of Hematology

      Volume: 107 Issue: 3 Pages: 311-319

    • DOI

      10.1007/s12185-017-2358-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional interleukin-33 receptors are expressed in early progenitor stages of allergy-related granulocytes.2017

    • Author(s)
      Tsuzuki H, Arinobu Y, Miyawaki K, Takaki A, Ota SI, Ota Y, Mitoma H, Akahoshi M, Mori Y, Iwasaki H, Niiro H, Tsukamoto H, Akashi K.
    • Journal Title

      Immunology

      Volume: 150 Pages: 64-73

    • NAID

      40021132441

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] アレルギーに関連する骨髄球系前駆細胞は機能的なIL-33受容体を発現する2017

    • Author(s)
      有信 洋二郎、續 啓史、赤司 浩一
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 67 Pages: 269-274

    • Related Report
      2016 Research-status Report
  • [Journal Article] 肥満細胞・好塩基球・好酸球とリウマチ性疾患2017

    • Author(s)
      有信 洋二郎
    • Journal Title

      九州リウマチ

      Volume: 37 Pages: 1-5

    • Related Report
      2016 Research-status Report
  • [Journal Article] 好塩基球の分化2016

    • Author(s)
      有信 洋二郎
    • Journal Title

      臨床検査

      Volume: 60 Pages: 820-824

    • Related Report
      2016 Research-status Report
  • [Journal Article] 関節単純X線とエコーの読み方2016

    • Author(s)
      綾野 雅宏、有信 洋二郎
    • Journal Title

      診断と治療

      Volume: 104 Pages: 1514-1519

    • Related Report
      2016 Research-status Report
  • [Presentation] コラーゲン誘導性関節炎モデルマウスの末梢組織おける自然リンパ球の量的・機能的変化についての検討2018

    • Author(s)
      桑原綾子、有信洋二郎、山田久方、大塚恭子、入野健佑、綾野雅宏、木本泰孝、三苫弘喜、赤星光輝、塚本浩、赤司浩一、堀内孝彦、新納宏昭
    • Organizer
      第62回 日本リウマチ学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨髄異形成症候群にみられる自己免疫疾患様症状の検討2018

    • Author(s)
      有信洋二郎、柏戸佑介、宮脇恒太、中山剛志、綾野雅宏、木本泰孝、三苫弘喜、赤星光輝、宮本敏浩、赤司浩一、堀内孝彦、新納宏昭
    • Organizer
      第62回 日本リウマチ学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊椎関節炎の診断における画像評価の有用性についての検討2018

    • Author(s)
      大塚 恭子、桑原 綾子、入野 健佑、有信 洋二郎、綾野 雅宏、木本 泰孝、三苫 弘喜、赤星 光輝、赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第55回 九州リウマチ学会
    • Related Report
      2017 Research-status Report
  • [Presentation] コラーゲン誘導関節炎モデルマウスにおける自然リンパ球の分化と機能に関する検討2017

    • Author(s)
      高木 綾子、有信 洋二郎、大塚 恭子、入野 健佑、押領司 大助、大田 友里、久本 仁美、綾野 雅宏、木本 泰孝、三苫 弘喜、赤星 光輝、塚本 浩、赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第61回 日本リウマチ学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 全身性エリテマトーデス患者における脳梗塞病変の臨床的検討2017

    • Author(s)
      入野 健佑、有信 洋二郎、綾野 雅宏、吾郷 哲朗、芝原 友也、河野 正太郎、高木 綾子、澤部 琢哉、木本 泰孝、三苫 弘喜、赤星 光輝、赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第61回 日本リウマチ学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Functional and Quantitative Changes of CCR6+type3 Innate Lymphoid Cells in Murine Collagen-Induced Arthritis2016

    • Author(s)
      Takaki A, Arinobu Y, Irino K, Tsuzuki H, Ota Y, Oryoji D, Ayano M, Kimoto Y, Mitoma H, Akahoshi M, Niiro H, Tsukamoto H, Horiuchi T, Akashi K
    • Organizer
      American College of Rheumatology 2016 Annual meeting
    • Place of Presentation
      Washington, DC
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] コラーゲン誘導性関節炎モデルマウスにおける自然リンパ球の検討2016

    • Author(s)
      高木 綾子、有信 洋二郎、入野 健佑、猪口 翔一朗、押領司 大助、大田 友里、久本 仁美、綾野 雅宏、木本 泰孝、三苫 弘喜、赤星 光輝、新納 宏昭、塚本 浩、赤司 浩一、堀内 孝彦
    • Organizer
      第44回 日本臨床免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report

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

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