Analysis of the pathogenesis of rheumatoid arthritis as infectious disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K20595
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Osaka University
• Principal Investigator: Takeda Kiyoshi 大阪大学, 大学院医学系研究科, 教授 (20309446)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 関節リウマチ / 腸内細菌

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.

Free Research Field

免疫学

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。