Analysis for the mechanism of sensorineural hearing loss caused by cochlear autoinflammation
Project/Area Number |
17K11324
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Otorhinolaryngology
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Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 免疫応答 / 蝸牛 / 難聴 / 自然免疫 |
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.
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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。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] 原著 当院で経験した中耳放線菌症3例の検討2019
Author(s)
中西啓, 水田邦博, 星野知之, 遠藤志織, 大和谷崇, 細川誠二, 峯田周幸
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Journal Title
耳鼻咽喉科・頭頸部外科
Volume: 91
Issue: 6
Pages: 483-488
DOI
ISSN
0914-3491, 1882-1316
Year and Date
2019-05-20
Related Report
Peer Reviewed
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[Journal Article] NLRP3 mutation and cochlear autoinflammation cause syndromic and nonsyndromic hearing loss DFNA34 responsive to anakinra therapy.2017
Author(s)
Nakanishi H, Kawashima Y, Kurima K, Chae JJ, Ross AM, Pinto-Patarroyo G, Patel SK, Muskett JA, Ratay JS, Chattaraj P, Park YH, Grevich S, Brewer CC, Hoa M, Kim HJ, Butman JA, Broderick L, Hoffman HM, Aksentijevich I, Kastner DL, Goldbach- Mansky R, Griffith AJ.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 114
Issue: 37
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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