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Analysis of the relationship between the pathology of rheumatoid arthritis and the intestinal flora.

Research Project

Project/Area Number 17K10002
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Narazaki Masashi  大阪大学, 医学系研究科, 特任教授(常勤) (00467573)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords関節リウマチ / 腸内細菌叢 / 炎症 / メタボローム / 免疫疾患 / 腸内細菌
Outline of Final Research Achievements

Changes in the intestinal flora and metabolites caused by the intestinal bacteria have various effects on the human body. In collaboration with Dr. Okada Y and others on campus, a whole-genome shotgun sequence analysis of the intestinal flora revealed that patients with rheumatoid arthritis are rich in multiple species belonging to the genus Prevotella, such as Prevotella denticola, in addition to P. copri. The genes related to the redox reaction were significantly reduced in patients with rheumatoid arthritis. In addition, serum metabolome analysis showed that the concentrations of nucleic acids such as UTP, ATP, GDP, and ADP were high and decreased after treatment, and these nucleic acids were disease-specific metabolites in patients with rheumatoid arthritis.

Academic Significance and Societal Importance of the Research Achievements

関節リウマチは免疫異常と慢性関節炎を特徴とし、関節機能障害に至る免疫疾患である。生物製剤の普及により予後は改善されてきたが、疾患の根本的原因は不明である。研究代表者らは過去に関節リウマチ患者から得られた腸内細菌P. copri菌をマウスへ投与すると関節炎が誘導されることを示した。本研究ではP. copri以外にもPrevotella属に属する複数の菌種が豊富に存在することを報告し、これらの菌株も関節リウマチの病態形成要因である可能性が示唆された。関節リウマチ血清では核酸濃度変化を指摘し、これまで臨床現場で測定されている炎症マーカー以外の新規疾患フォローマーカーとなる可能性がある。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2020 2019 2018 2017

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 13 results) Presentation (6 results)

  • [Journal Article] Pristane/Hypoxia (PriHx) Mouse as a Novel Model of Pulmonary Hypertension Reflecting Inflammation and Fibrosis2020

    • Author(s)
      Mori Hiroyoshi、Ishibashi Tomohiko、Inagaki Tadakatsu、Okazawa Makoto、Masaki Takeshi、Asano Ryotaro、Manabe Yusuke、Ohta-Ogo Keiko、Narazaki Masashi、Ishibashi-Ueda Hatsue、Kumanogoh Atsushi、Nakaoka Yoshikazu
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 7 Pages: 1163-1172

    • DOI

      10.1253/circj.CJ-19-1102

    • NAID

      130007864283

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2020-06-25
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recovery from prolonged thrombocytopenia in patients with TAFRO syndrome: case series and literature review2020

    • Author(s)
      Yamaguchi Yuta、Maeda Yuichi、Shibahara Takayuki、Nameki Shinichiro、Nakabayashi Akihiko、Komuta Kiyohide、Mizuno Yumiko、Yagita Mayu、Manabe Yusuke、Morita Takayoshi、Nishide Masayuki、Watanabe Akane、Takamatsu Hyota、Nishida Sumiyuki、Hirano Toru、Shima Yoshihito、Narazaki Masashi、Kumanogoh Atsushi
    • Journal Title

      Modern Rheumatology Case Reports

      Volume: 4 Issue: 2 Pages: 302-309

    • DOI

      10.1080/24725625.2020.1717747

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of SAPHO syndrome with the lesions limited to the skull2020

    • Author(s)
      Oguro Eri、Kato Yasuhiro、Takamatsu Hyota、Narazaki Masashi、Kumanogoh Atsushi
    • Journal Title

      Rheumatology Advances in Practice

      Volume: 4 Issue: 2 Pages: 1-2

    • DOI

      10.1093/rap/rkaa034

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased levels of plasma nucleotides in patients with rheumatoid arthritis2020

    • Author(s)
      Kishikawa T、Maeda Y、Nii T、Arase N、Hirata J、Suzuki K、Yamamoto K、Masuda T、Ogawa K、Tsuji S、Matsushita M、Matsuoka H、Yoshimura M、Tsunoda S、Ohshima S、Narazaki M、Ogata A、Saeki Y、Inohara H、Kumanogoh A、Takeda K、Okada Y
    • Journal Title

      International Immunology

      Volume: 33 Issue: 2 Pages: 119-124

    • DOI

      10.1093/intimm/dxaa059

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tet DNA demethylase is required for plasma cell differentiation by controlling expression levels of IRF42020

    • Author(s)
      Fujii, K. Tanaka, S. Hasegawa, T. Narazaki, M. Kumanogoh, A. Koseki, H. Kurosaki, T. Ise, W.
    • Journal Title

      International Immunology

      Volume: 32 Issue: 10 Pages: 683-690

    • DOI

      10.1093/intimm/dxaa042

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Historical overview of the interleukin-6 family cytokine2020

    • Author(s)
      Kang Sujin、Narazaki Masashi、Metwally Hozaifa、Kishimoto Tadamitsu
    • Journal Title

      Journal of Experimental Medicine

      Volume: 217 Issue: 5 Pages: 1-10

    • DOI

      10.1084/jem.20190347

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population2020

    • Author(s)
      Kishikawa T, Maeda Y, Nii T, Motooka D, Matsumoto Y, Matsushita M, Matsuoka H, Yoshimura M, Kawada S, Teshigawara S, Oguro E, Okita Y, Kawamoto K, Higa S, Hirano T, Narazaki M, Ogata A, Saeki Y, Nakamura S, Inohara H, Kumanogoh A, Takeda K, Okada Y.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 79(1) Issue: 1 Pages: 103-111

    • DOI

      10.1136/annrheumdis-2019-215743

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors2019

    • Author(s)
      Nakai Akiko、Fujimoto Jun、Miyata Haruhiko、Stumm Ralf、Narazaki Masashi、Schulz Stefan、Baba Yoshihiro、Kumanogoh Atsushi、Suzuki Kazuhiro
    • Journal Title

      Journal of Experimental Medicine

      Volume: 216 Issue: 7 Pages: 1630-1647

    • DOI

      10.1084/jem.20181494

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting Interleukin-6 Signaling in Clinic2019

    • Author(s)
      Kang Sujin、Tanaka Toshio、Narazaki Masashi、Kishimoto Tadamitsu
    • Journal Title

      Immunity

      Volume: 50 Issue: 4 Pages: 1007-1023

    • DOI

      10.1016/j.immuni.2019.03.026

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-receptor activator of nuclear factor κB ligand antibody treatment increases osteoclastogenesis-promoting IL-8 in patients with rheumatoid arthritis2019

    • Author(s)
      Morita Takayoshi、Shima Yoshihito、Fujimoto Kosuke、Tsuboi Hideki、Saeki Yukihiko、Narazaki Masashi、Ogata Atsushi、Kumanogoh Atsushi
    • Journal Title

      International Immunology

      Volume: 31 Issue: 5 Pages: 277-285

    • DOI

      10.1093/intimm/dxz009

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Two-Faced Cytokine IL-6 in Host Defense and Diseases2018

    • Author(s)
      Narazaki M, Kishimoto T
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 19(11) Issue: 11 Pages: 3528-3528

    • DOI

      10.3390/ijms19113528

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin (IL-6) Immunotherapy.2018

    • Author(s)
      Tanaka T, Narazaki M, Kishimoto T
    • Journal Title

      Cold Spring Harb Perspect Biol.

      Volume: 10(8) Issue: 8 Pages: a028456-a028456

    • DOI

      10.1101/cshperspect.a028456

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clonal evolution and antigen recognition of anti-nuclear antibodies in acute systemic lupus erythematosus.2017

    • Author(s)
      Sakakibara S., Arimori T., Yamashita K., et al
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 16428-16428

    • DOI

      10.1038/s41598-017-16681-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role and therapeutic targeting of IL-6 in rheumatoid arthritis.2017

    • Author(s)
      Narazaki M, Tanaka T, Kishimoto T
    • Journal Title

      Expert Rev Clin Immunol

      Volume: 13 Issue: 6 Pages: 535-551

    • DOI

      10.1080/1744666x.2017.1295850

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 炎症が鎮静化した関節リウマチ患者の疼痛症状と関連する液性因子の検討2020

    • Author(s)
      森田貴義,石塚智子,西出真之,前田悠一,平野亨,嶋良仁,楢崎雅司,熊ノ郷淳
    • Organizer
      第64回日本リウマチ学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マスサイトメトリーを用いた全身性エリテマトーデス患者末梢血中の特徴的集団の検出2020

    • Author(s)
      梶原亜紀子,森田貴義,加藤保宏,小中八郎,渡邉あかね,西出 之,前田悠一,高松漂太, 平野亨,嶋良仁,楢崎雅司,熊ノ郷淳
    • Organizer
      第64回日本リウマチ学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マスサイトメーターCyTOFを用いたIL-6自己抗体産生患者の免疫動態解析2020

    • Author(s)
      森田貴義, 真鍋侑資, 小中八郎, 加藤保宏, 梶原亜紀子, 楢崎雅司, 熊ノ郷淳
    • Organizer
      第64回日本リウマチ学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 副鼻腔腫瘤と肺多発結節影を認め,多発血管炎性肉芽腫症との鑑別を要した医原性免疫不全関連リンパ増殖性疾患の一例2020

    • Author(s)
      行木紳一郎,加藤保宏,高松漂太,西出真之, 小黒英里,Tansri Wibowo,葛谷憲太郎,原侑紀, 前田悠一,楢崎雅司,熊ノ郷淳
    • Organizer
      第64回日本リウマチ学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 2種類の異なる経過を辿る肺陰影を認めた抗MDA5抗体陽性皮膚筋炎の一例2020

    • Author(s)
      原侑紀, 前田悠一, 小黒英里, 行木紳一郎, 葛谷憲太郎, WibowoTansri, 高松漂太, 西田純幸, 楢崎雅司, 熊ノ郷淳
    • Organizer
      第64回日本リウマチ学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 頭蓋骨からCutibacterium acnesを検出したSAPHO症候群の一例2020

    • Author(s)
      小黒英里, 加藤保宏, 行木紳一郎, 葛谷憲太郎, Wibowo Tansri, 原侑紀, 前田悠一, 高松漂太, 楢崎雅司, 熊ノ郷淳
    • Organizer
      第64回日本リウマチ学会
    • Related Report
      2020 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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