Intravital imaging of anti-fungal immunity focusing on the role of epithelial cells in the skin

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17770
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kyoto University
• Principal Investigator: Murata Teruasa 京都大学, 医学研究科, 助教 (40838801)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: カンジダ / 皮膚角化細胞 / 細胞死 / 真菌感染 / 体細胞変異 / 遺伝性角化症 / KID症候群 / 魚鱗癬症候群

Outline of Final Research Achievements

Candida, the major fungus infecting humans, is known to be eliminated by leukocytes. However, KID syndrome is complicated by chronic cutaneous candidiasis despite mutations in the GJB2 gene, which is unlikely to be involved in leukocyte function, and the cause of the disease is unknown. In this study, we analyzed the unusual phenomenon of somatic mutations appearing after the healing of cutaneous candidiasis in patients with KID syndrome and conducted experiments using a mouse model of KID syndrome. The results revealed that GJB2 mutations in skin keratinocytes are responsible for the susceptibility to Candida infection.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

カンジダは高齢者や免疫力の低下した人に重篤な日和見感染を起こす真菌であり、皮膚は人体への侵入門戸の一つである。これまで白血球の機能に注目した研究が蓄積されてきたが、上皮細胞の関わりを直接示すヒトの疾患はなかった。本研究で解析した体細胞変異は、皮膚角化細胞がカンジダへの抵抗力に関わる可能性を強く示唆するものである。皮膚に限らず上皮細胞の働きに着目した、カンジダ感染症の予防・治療法の開発につながる可能性がある。