Sun Qiyang, Sun Xiaomei, Zhao Mengqi, Wen Weiping, Wei Fanqin
Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Department of Otorhinolaryngology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
ORL J Otorhinolaryngol Relat Spec. 2025;87(1):45-56. doi: 10.1159/000545134. Epub 2025 Mar 8.
Inflammaging is a key mechanism in presbycusis. CX3CL1-CX3CR1 pathway is critical for cochlear macrophage-hair cell cross-talk. However, its role in inflammaging remains unclear.
To investigate the role of CX3CL1-CX3CR1 signaling in cochlear inflammaging, single-cell RNA sequencing (scRNA-seq) data from young and aged mouse cochleae were analyzed to map CX3CL1-CX3CR1 distribution and aging-related trends. Findings were validated with immunofluorescence, real-time quantitative polymerase chain reaction, and Western blot. A migration assay assessed CX3CL1-CX3CR1's influence on macrophage migration and inflammation.
scRNA-seq analysis showed CX3CL1 mainly located in the basal cells of stria vascularis (SV), while CX3CR1 and TNF-a mainly located in macrophages. The mRNA levels of CX3CL1, CX3CR1, and TNF-a in the SV significantly upregulated in aged mice. The Western blot showed similar trends, but only the upregulation of soluble CX3CL1 was statistically significant. Exogenous CX3CL1 significantly promoted BV2 cell migration and TNF-a secretion induced by LPS, while such effects were canceled in BV2 cells with CX3CR1 interfered.
The overexpression of CX3CL1 in the basal cells of the SV with aging may be a trigger point for activating the local inflammatory microenvironment in age-related hearing loss, but it still requires further in vivo intervention experiments for validation.
炎症衰老（inflammaging）是老年性聋的关键机制。CX3CL1 - CX3CR1信号通路对于耳蜗巨噬细胞 - 毛细胞的相互作用至关重要。然而，其在炎症衰老中的作用尚不清楚。
为研究CX3CL1 - CX3CR1信号在耳蜗炎症衰老中的作用，分析了年轻和老年小鼠耳蜗的单细胞RNA测序（scRNA - seq）数据，以绘制CX3CL1 - CX3CR1的分布及与衰老相关的趋势。研究结果通过免疫荧光、实时定量聚合酶链反应和蛋白质免疫印迹法进行验证。迁移实验评估了CX3CL1 - CX3CR1对巨噬细胞迁移和炎症的影响。
scRNA - seq分析显示，CX3CL1主要位于血管纹（SV）的基底细胞中，而CX3CR1和肿瘤坏死因子 - a（TNF - a）主要位于巨噬细胞中。老年小鼠SV中CX3CL1、CX3CR1和TNF - a的mRNA水平显著上调。蛋白质免疫印迹法显示了类似的趋势，但只有可溶性CX3CL1的上调具有统计学意义。外源性CX3CL1显著促进了脂多糖（LPS）诱导的BV2细胞迁移和TNF - a分泌，而在CX3CR1受到干扰的BV2细胞中这种作用被消除。
随着衰老，SV基底细胞中CX3CL1的过表达可能是激活年龄相关性听力损失局部炎症微环境的触发点，但仍需要进一步的体内干预实验来验证。
