Elucidation of pathological control mechanism of rheumatoid arthritis by interaction between enteric nervous system and immune system and development of novel treatment

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08917
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: Maezawa Reika 獨協医科大学, 医学部, 准教授 (20322406)
• Co-Investigator(Kenkyū-buntansha): 有馬 雅史 獨協医科大学, 医学部, 教授 (00202763) ; 幡野 雅彦 千葉大学, 大学院医学研究院, 教授 (20208523) ; 倉沢 和宏 獨協医科大学, 医学部, 教授 (30282479)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 関節リウマチ / 腸管神経 / 腸管免疫 / NCX

Outline of Final Research Achievements

It has been presumed that intestinal immune abnormalities caused by changes in the intestinal microbiota (dysbiosis) are involved in the pathogenesis of rheumatoid arthritis. In this study, we analyzed the role of the Ncx gene in autoimmune arthritis using Ncx-KO mice and SKG mice, a model of autoimmune disease, focusing on the presence of dysbiosis in the intestinal tract with increased nitric oxide production in mice due to Ncx gene deletion. Contrary to expectations, Ncx deficiency resulted in milder arthritis in SKG-mice. This study suggests that the Ncx gene is involved in the regulation of the pathogenesis of autoimmune arthritis in addition to dysbiosis. However, the mechanism is still not fully understood, and further studies are ongoing.

Free Research Field

自己免疫疾患　リウマチ性疾患　膠原病

Academic Significance and Societal Importance of the Research Achievements

本研究において，マウスの関節炎モデルの解析により腸管の一酸化窒素産生神経細胞の増加が関節リウマチ様関節炎の重症度に関与することや，腸内の環境変化が過剰免疫システムの誘導に関与すること可能性が示唆された．今までに，関節リウマチの発症について腸内細菌叢と一酸化窒素の腸内産生を関連付けて着目した研究は国内外において報告されていない．一酸化窒素の産生の機能調節が新規の治療開発につながる可能性に着目した本研究の成果は，関節リウマチなど自己免疫性関節炎の新規治療法の開発に大いに貢献し，さらに様々な免疫性疾患の病態の分子メカニズムの解明や新規分子標的治療法の開発へとつながることが期待される．