| Project/Area Number |
16K11178
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山本 典生 京都大学, 医学研究科, 准教授 (70378644)
田浦 晶子 藍野大学, 医療保健学部, 教授 (70515345)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 蝸牛 / 組織マクロファージ / 免疫 / 発生 / 先天性難聴 / 感音難聴 / 内耳 / マクロファージ / 聴覚 / 耳鼻咽喉科学 / 免疫学 / 発生学 / 神経科学 |
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| Outline of Final Research Achievements |
In order to investigate the spatial and temporal pattern of distribution of resident macrophage in the developing cochlea, we analyzed the mouse embryonic cochleae from E9.5 and onward. Resident macrophages expressing Iba1 emerge the mesenchyme surrounding the otocyst as early as E10.5 and then are distributed in the whole cochlea including the spiral ligament, spiral ganglion, and stria vasuclaris. Next we studied the proliferation capacity of cochlear resident macrophages using immunohistochemistry for Ki67 or pHH3, suggesting that self-maintenance of resident macrophages by in situ proliferation. Finally, using Csf1r-null mice, we demonstrated that resident macrophages in the mouse developing cochlea have two distinct origins and characteristics; ones dependent on Csf1r-signaling with yolk sac origin, and the others independent on Csf1r-signaling with fetal liver origin.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において明らかにされた蝸牛組織マクロファージの発生学的由来や組織内分布は、蝸牛組織マクロファージの機能解明する研究の起点となる。先天性サイトメガロウイルス感染をはじめとする感染性の先天性難聴は、その病態に免疫機構の関与が示唆されるものの詳細は不明であり、未だ治療も確立されていない。蝸牛の免疫機構の理解により、感染性の先天性難聴を含めた内耳疾患における組織マクロファージを標的とした治療の開発へと発展する可能性がある。
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