Analysis of the pathogenesis of rheumatoid arthritis as infectious disease
| Project/Area Number |
20K20595
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| Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
Takeda Kiyoshi 大阪大学, 大学院医学系研究科, 教授 (20309446)
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2022: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2021: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2020: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
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| Keywords | 関節リウマチ / 腸内細菌 / プレボラ細菌 / 免疫 |
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| Outline of Research at the Start |
これまでに関節リウマチ患者の腸内細菌叢でPrevotella copriが増加していること、モデルマウスを用いて関節リウマチ患者由来のP. copriが関節炎の発症に関与することを示した。しかし、P. copriは、穀物や繊維類を主食とする地域の健常者の主たる腸内細菌叢である。そこで、患者及び健常人よりP. copriを単離し、そのゲノムを比較するとともに、関節炎の誘導能をマウス関節炎モデルを用いて解析する。さらに、関節炎を誘導する病原因子の同定を行い、関節リウマチが感染症の一つとして発症しうることを証明する。
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| Outline of Final Research Achievements |
We found that a P. copri strain isolated from the faeces of rheumatoid arthritis patients (RA-P. copri) induced more severe arthritis than P. copri from healthy individuals (HC-P. copri) in two different mouse arthritis models. As a molecular mechanism, we found that RA-P. copri strongly activated dendritic cells and induced more Th17 cells. Furthermore, whole genome sequencing of RA-P. copri and HC-P. copri was performed, which revealed that a genomic region of approximately 100 kb was inserted in the RA-P. copri strain. This genomic region had sequences specific to the transposon. These results indicate that RA-P. copri acquired this region by horizontal gene transfer. The absence of this region in HC-P. copri suggests that it may be responsible for pathogenicity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、関節リウマチ患者には、関節炎を強く誘導するP. copri(RA-P. copri)が腸管内に多く定着していること、RA-P. copriには、健常人のP. copri (HC-P. copri)にはないゲノム領域が挿入されていることを見出した。本領域はHC-P. copriには存在しないことから、病原性を担っていることが示唆された。以上の結果は、関節リウマチが病原性を有するプレボテラ菌の腸管内定着（感染）により発症することを示しており、今後、本病原性プレボテラ菌を標的とした関節リウマチの治療、予防法の開発につながるものと考えられ、その学術的、社会的意義は大きいものと考えられる。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Longitudinal alterations of the gut mycobiota and microbiota on COVID-19 severity2022
Author(s)
Maeda Yuichi、Motooka Daisuke、Kawasaki Takahiro、Oki Hiroya、Noda Yoshimi、Adachi Yuichi、Niitsu Takayuki、Okamoto Shota、Tanaka Kentaro、Fukushima Kiyoharu、Amiya Saori、Hara Reina、Oguro-Igashira Eri、Matsuki Takanori、Hirata Haruhiko、Takeda Yoshito、Kida Hiroshi、Kumanogoh Atsushi、Nakamura Shota、Takeda Kiyoshi
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Journal Title
BMC Infectious Diseases
Volume: 22
Issue: 1
Pages: 572-572
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The ATP-hydrolyzing ectoenzyme E-NTPD8 attenuates colitis through modulation of P2X4 receptor-dependent metabolism in myeloid cells.2021
Author(s)
Tani H, Li B, Kusu T, Okumura R, Nishimura J, Okuzaki D, Motooka D, Arakawa S, Yoshihara T, Ogino T, Tsai SH, Furuta Y, Muneta M, Nakamura S, Fukusaki E, Yamamoto K, Yagita H, Kayama H and Takeda K
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 118
Issue: 39
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Oral intake of silica nanoparticles exacerbates intestinal inflammation.2021
Author(s)
Ogawa T, Okumura R, Nagano K, Minemura T, Izumi M, Motooka D, Nakamura S, Iida T, Maeda Y, Kumanogoh A, Tsutsumi Y, Takeda K
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Journal Title
Biochem Biophys Res Commun
Volume: 534
Pages: 540-546
DOI
Related Report
Peer Reviewed
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