Effects of Central Tolerance on Pathophysiology in the Thymus of a Mouse Model of Kawasaki Disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15901
• 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: Shiga University of Medical Science
• Principal Investigator: Sato Tomomi 滋賀医科大学, 医学部, 特任助教 (50874921)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 川崎病 / FK565 / 胸腺

Outline of Final Research Achievements

We analyzed the thymus gland in FK565-induced Kawasaki disease model mice; although FK565 mice are usually analyzed on the seventh day after immunization, we decided to use the thymus gland on the first day after immunization for analysis because the thymus gland atrophied after seven days, making analysis difficult. Flow cytometric analysis showed that CD4-positive T cells and CD8-positive T cells were decreased in the Kawasaki disease model mice, but double positive T cells were especially decreased, suggesting a decreased function of the thymic medullary epithelium. Immunostaining showed that medullary epithelial cells were also seen in Kawasaki disease model mice, but double positive T cells in the medulla were decreased.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

川崎病モデルマウスの冠動脈炎発症に、胸腺トレランスの破綻が関与している可能性について調べた。川崎病は日本人小児に好発し、無治療では高率に冠動脈疾患を引き起こす。冠動脈の炎症により冠動脈瘤を来すと若年性の心筋梗塞に至ることもある。現在の川崎病治療は、ガンマグロブリン静脈注射ややステロイド内服、インフリキシマブ静脈注射など高価で重大な副作用を伴う治療薬が用いられており、胸腺の分子に直接影響するような安価で安全な治療薬の開発に繋がる可能性がある。