Generation of an animal model and identification of therapeutic targets for auto-inflammatory syndrome

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10917
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: Miyamoto Kana 慶應義塾大学, 医学部(信濃町), 研究員 (60464997)
• Research Collaborator: OIKE Takatsugu
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 関節疾患

Outline of Final Research Achievements

Auto-inflammatory syndrome is a disease characterized by systemic inflammation in tissues such as major joints, and is distinct from rheumatoid arthritis (RA), which exhibits minor joint inflammation. However, since auto-inflammatory syndrome is a rare disease, and the appropriate animal models were not generated, underlying pathological mechanisms have not been clarified nor are treatment strategies established. In this study, we successfully established a new mouse model in which IL-1 signaling was conditionally activated in adult mice (cTg), and observed phenotypes similar to those seen in auto-inflammatory syndrome patients. We found that levels of serum IL-6 and IL-17 were elevated and Stat3 was activated in joints of cTg mice. Phenotypes seen in cTg mice were ameliorated by crossing cTg mice with either IL-6 KO, IL-17 KO or Stat3 cKO mice. Thus, we concluded that IL-6, IL-17 and Stat3 all represent potential therapeutic targets for Auto-inflammatory syndrome.

Free Research Field

整形外科学、血液・膠原病学

Academic Significance and Societal Importance of the Research Achievements

自己炎症症候群は大関節優位の関節炎を発症するなど、小関節優位の関節炎を発症する関節リウマチ（RA）とは区別される。しかし、自己炎症症候群は患者数が少ないことや動物モデルが樹立されていないこともあり、その病態解明や治療法の開発は進んでいなかった。本研究では、自己炎症症候群の表現型を再現する動物モデルを新規に樹立し、その解析からIL-6、IL-17およびStat3が自己炎症症候群の治療標的となり得ることを示し得た点で、学術的また社会的意義があると考えている。