耳蜗巨噬细胞在老年性聋中的作用：炎性衰老、神经炎症及治疗调控靶点

文献信息

中文摘要

背景： 年龄相关神经退行性疾病和年龄相关听力损失在全球范围内的患病率不断上升。免疫细胞是连接这些疾病的新型介质，其通过慢性炎症和适应不良性修复等共同机制发挥作用。在耳蜗中，驻留巨噬细胞和浸润免疫细胞对损伤、噪声暴露和衰老作出反应，采用活化表型，破坏突触完整性、损害髓鞘形成，并促进毛细胞和神经元丢失。同样，在中枢神经系统中，小胶质细胞（大脑的驻留免疫细胞）经历与年龄和疾病相关的致敏，其特征为过度的炎症反应、补体激活和细胞碎片清除受损。新出现的证据表明，耳蜗巨噬细胞和中枢神经系统小胶质细胞共享转录程序和信号通路。重要的是，这些免疫细胞在适当调控下也可作为修复和再生的关键调节因子，采用促再生表型促进组织恢复而非损伤。随着听力损失日益被认为是神经退行性疾病的促成风险因素，加深我们对内耳年龄相关免疫反应及免疫细胞调控机制的理解，可能有助于减轻这一风险，同时揭示这些相关疾病过程之间的共同治疗靶点。

英文摘要

Age-related neurodegenerative diseases and age-related hearing loss are increasing in prevalence globally. Immune cells are novel mediators linking these diseases through shared mechanisms of chronic inflammation and maladaptive repair. In the cochlea, resident macrophages and infiltrating immune cells respond to injury, noise exposure, and aging by adopting activated phenotypes that disrupt synaptic integrity, impair myelination, and promote hair cell and neuronal loss. Similarly, in the central nervous system, microglia, the resident immune cells of the brain undergo age- and disease-associated priming, characterized by exaggerated inflammatory responses, complement activation, and impaired clearance of cellular debris. Emerging evidence suggests that cochlear macrophages and CNS microglia share transcriptional programs and signaling pathways. Importantly, these immune cells also serve as key regulators of repair and regeneration when appropriately modulated, adopting pro-regenerative phenotypes that promote tissue recovery rather than injury. As hearing loss is increasingly recognized as a contributing risk factor for neurodegenerative disease, deepening our understanding of age-related immune responses within the inner ear and the mechanisms governing immune cell modulation may help mitigate this risk while uncovering shared therapeutic targets across these related disease processes.