Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Department of Otolaryngology-Head and Neck Surgery, Osaka Metropolitan University, Abeno-ku, Osaka, Japan.
Sci Rep. 2024 Jan 2;14(1):62. doi: 10.1038/s41598-023-50634-y.
The percentage of macrophage subpopulations based on their origins in the adult cochlea remains unclear. This study aimed to elucidate the origins of cochlear macrophages during the onset phase and development of auditory function. We used three types of mice: wildtype ICR mice, colony-stimulating factor 1 receptor (Csf1r)-deficient mice, and Ms4a3Cre-Rosa tdTomato (Ms4a3) transgenic mice. Macrophages were labeled with ionized calcium-binding adapter molecule 1 (Iba1), which is specific to more mature macrophages, and CD11b, which is specific to monocyte lineage. We investigated the spatial and temporal distribution patterns of resident macrophages in the cochlea during the postnatal and early adult stages. During the adult stages, the rate of monocytes recruited from the systemic circulation increased; moreover, Iba1/CD11b cochlear macrophages gradually decreased with age. Fate mapping of monocytes using Ms4a3 transgenic mice revealed an increased proportion of bone marrow-derived cochlear macrophages in the adult stage. Contrastingly, the proportion of yolk sac- and fetal liver-derived tissue-resident macrophages decreased steadily with age. This heterogeneity could be attributed to differences in environmental niches within the tissue or at the sub-tissue levels. Future studies should investigate the role of cochlear macrophages in homeostasis, inflammation, and other diseases, including infection, autoimmune, and metabolic diseases.
基于其在成年耳蜗中的起源，巨噬细胞亚群的百分比仍不清楚。本研究旨在阐明听觉功能起始阶段和发育过程中耳蜗巨噬细胞的起源。我们使用了三种类型的小鼠：野生型 ICR 小鼠、集落刺激因子 1 受体（Csf1r）缺陷型小鼠和 Ms4a3Cre-Rosa tdTomato（Ms4a3）转基因小鼠。巨噬细胞用离子钙结合衔接分子 1（Iba1）和 CD11b 进行标记，Iba1 特异性标记更成熟的巨噬细胞，CD11b 特异性标记单核细胞谱系。我们研究了在出生后和成年早期，驻留在耳蜗中的固有巨噬细胞的时空分布模式。在成年期，来自全身循环的单核细胞募集率增加；此外，Iba1/CD11b 耳蜗巨噬细胞随着年龄的增长逐渐减少。使用 Ms4a3 转基因小鼠对单核细胞进行的命运图谱分析显示，成年期骨髓来源的耳蜗巨噬细胞比例增加。相比之下，卵黄囊和胎肝来源的组织驻留巨噬细胞的比例随着年龄的增长而稳步下降。这种异质性可能归因于组织内或亚组织水平上的环境小生境的差异。未来的研究应探讨耳蜗巨噬细胞在稳态、炎症和其他疾病（包括感染、自身免疫和代谢疾病）中的作用。
