Immune system dysregulation is increasingly being attributed to the development of a multitude of neurodegenerative diseases. This, in large part, is due to the delicate relationship that exists between neurons in the central nervous system (CNS) and peripheral nervous system (PNS), and the resident immune cells that aid in homeostasis and immune surveillance within a tissue. Classically, the inner ear was thought to be immune privileged due to the presence of a blood-labyrinth barrier. However, it is now well-established that both vestibular and auditory end organs in the inner ear contain a resident (local) population of macrophages which are the phagocytic cells of the innate-immune system. Upon cochlear sterile injury or infection there is robust activation of these resident macrophages and a predominant increase in the numbers of macrophages as well as other types of leukocytes. Despite this, the source, nature, fate and functions of these immune cells during cochlear physiology and pathology remains unclear. Migration of local macrophages and infiltration of bone-marrow derived peripheral blood macrophages into the damaged cochlea occur through various signaling cascades, mediated by release of specific chemical signals from damaged sensory and non-sensory cells of the cochlea. One such signaling pathway is CX3CL1-CX3CR1, or fractalkine (FKN) signaling, a direct line of communication between macrophages and sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) of the cochlea. Despite the known importance of this neuron-immune axis in CNS function and pathology, until recently it was not clear whether this signaling axis played a role in macrophage chemotaxis and SGN survival following cochlear injury. In this review, we will explore the importance of innate immunity in neurodegenerative disease development, specifically focusing on the regulation of the CX3CL1-CX3CR1 axis, and present evidence for a role of FKN signaling in cochlear neuroprotection.

中文翻译：

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对螺旋神经节神经元丢失的先天免疫：Fractalkine 信号传导在受伤耳蜗中的神经保护作用

免疫系统失调越来越多地归因于多种神经退行性疾病的发展。这在很大程度上是由于中枢神经系统 (CNS) 和外周神经系统 (PNS) 中的神经元与有助于组织内稳态和免疫监视的常驻免疫细胞之间存在微妙的关系。传统上，由于血迷宫屏障的存在，内耳被认为具有免疫特权。然而，现在已经确定内耳中的前庭和听觉终末器官都含有常驻（局部）巨噬细胞群，这些巨噬细胞是先天免疫系统的吞噬细胞。在耳蜗无菌损伤或感染后，这些常驻巨噬细胞被强烈激活，巨噬细胞和其他类型的白细胞数量显着增加。尽管如此，这些免疫细胞在耳蜗生理和病理过程中的来源、性质、命运和功能仍不清楚。局部巨噬细胞的迁移和骨髓来源的外周血巨噬细胞向受损耳蜗的浸润通过各种信号级联发生，由耳蜗受损感觉和非感觉细胞释放特定化学信号介导。一种这样的信号通路是 CX3CL1-CX3CR1 或 fractalkine (FKN) 信号，这是巨噬细胞与感觉内毛细胞 (IHC) 和耳蜗螺旋神经节神经元 (SGN) 之间的直接通信线路。尽管这种神经元免疫轴在 CNS 功能和病理学中的重要性众所周知，但直到最近还不清楚该信号轴是否在巨噬细胞趋化性和耳蜗损伤后 SGN 存活中发挥作用。在这篇综述中，我们将探讨先天免疫在神经退行性疾病发展中的重要性，特别关注 CX3CL1-CX3CR1 轴的调节，并提供 FKN 信号在耳蜗神经保护中的作用的证据。