Drug discovery targeting Tet3 for refractory rheumatoid arthritis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Nakano Kazuhisa 産業医科大学, 医学部, 講師 (50406500)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 関節リウマチ / サイトカイン / 滑膜 / DNAメチル化 / エピゲノム

Outline of Final Research Achievements

In rheumatoid arthritis (RA), which is a representative autoimmune disease, it is assumed that epigenetic alterations occur in the synovium under the inflammatory environment, resulting in the acquisition of a trait that is more prone to joint destruction and refractory to treatment. In a series of studies, we found that the DNA demethylase TET3 was induced by inflammatory cytokines including TNFα and altered the expression of many genes. As an epigenetic gate-keeper in the pathogenesis of RA, TET3 may play a key role in prolonging inflammation.

Free Research Field

関節リウマチ

Academic Significance and Societal Importance of the Research Achievements

近年、関節リウマチ（RA）においては、生物学的製剤やJAK阻害剤などの分子標的薬の登場により、寛解を目指した治療が可能となったが、分子標的療法でもその３割から４割は治療抵抗性を示し、治療経過とともに難治化する。今回の研究成果は、TET3を標的としたRA滑膜におけるエピゲノム異常の是正が、RA治療のブレークスルーとなりうる可能性を示唆した。