Analysis for the mechanism of sensorineural hearing loss caused by cochlear autoinflammation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11324
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Nakanishi Hiroshi 浜松医科大学, 医学部, 助教 (20444359)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 免疫応答 / 蝸牛 / 難聴

Outline of Final Research Achievements

Gain of function mutations of NLRP3 induce the activation of NLRP3 inflammasome, resulting in the secretion of proinflammatory cytokine, interleukin-1 beta, to cause systemic inflammatory diseases, cryopyrin associated periodic syndromes. We revealed that a gain of function mutation of NLRP3 also cause non-syndromic hearing loss. We hypothesized that the hearing loss was caused by the activation of NLRP3 inflammasome mainly in the cochleae. We revealed that NLRP3 inflammasome was activated in tissue-resident macrophage-like cells in the wild type mouse cochleae, supporting the hypothesis.

Free Research Field

耳鼻咽喉科学

Academic Significance and Societal Importance of the Research Achievements

蝸牛には組織マクロファージなどの免疫担当細胞は存在せず、難聴にも関与しないと考えられてきた。この研究は、蝸牛内に組織マクロファージが存在し、その細胞内に能動免疫の中心的役割を果たすNLRP3インフラマソームが存在すること、さらに蝸牛内炎症が難聴に関与することを明らかにした点で大変画期的であると思われる。この研究成果は英文誌に掲載された。