2019 Fiscal Year Final Research Report

Csf1r signaling plays a key role on origin and differentiation of resident macrophages in the developing cochlea

Research Project

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Project/Area Number	16K11178
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Otorhinolaryngology
Research Institution	Kyoto University
Principal Investigator	OKANO Takayuki 京都大学, 医学研究科, 助教 (60642931)
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)
Project Period (FY)	2016-04-01 – 2020-03-31
Keywords	蝸牛 / 組織マクロファージ / 免疫 / 発生
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.
Free Research Field	耳鼻咽喉科学
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。