Mechanisms of caspase-1-independent cell death induced by NLRP3 and NLRC4 disease-associated variants

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17293
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto University
• Principal Investigator: Izawa Kazushi 京都大学, 医学研究科, 助教 (90634931)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 自己炎症性疾患 / NLRC4異常症 / 家族性地中海熱 / MEFV / インフラマソーム

Outline of Final Research Achievements

Both cryopyrin-associated periodic fever syndrome and NLRC4- associated diseases cause inflammasome activation, but the pathogenesis is different with IL-1 beta and IL-18, respectively. First, to analyze the inflammatory mechanism of NLRC4- associated diseases, we constructed a functional analysis system using NLRC4 gene mutations. This system made it possible to determine whether the mutation was disease-related or not. In addition, there has been no simple method to distinguish disease association of MEFV gene variants in familial Mediterranean fever, an inflammasome-associated disease. In this study, we succeeded in developing a functional analysis system for MEFV variants.

Free Research Field

自己炎症性疾患

Academic Significance and Societal Importance of the Research Achievements

自己炎症性疾患の診療においては、遺伝子検査を行い診断が確定となる。病原性不明な遺伝子変異が検出された際には、臨床症状や疫学的情報の他に、機能解析等を行い、その病原性を判定する。NLRC4異常症と家族性地中海熱において遺伝子変異が検出された際にその病原性を判定する解析系を構築することができ、自己炎症性診療においてより精度の高い診断を行うことが可能になった。