Immune Cell Biology in Peripheral Nervous System Injury

Background: The peripheral nervous system (PNS) exhibits remarkable regenerative capability after injury. PNS regeneration relies on neurons themselves as well as a variety of other cell types, including Schwann cells, immune cells, and non-neuronal cells. Objectives: This paper focuses on summarizing the critical roles of immune cells (SCs) in the injury and repair processes of the PNS. Results: During peripheral nerve injury, macrophages infiltrate the site under the induction of various cytokines, primarily accumulating at the dorsal root ganglia (DRG) and the nerve distal to the injury site, with only a small number detected at the nerve proximal to the injury site. The phenotype of macrophages during injury remains controversial, but recent single-cell sequencing analyses may provide new insights. In peripheral nervous system injury, macrophages participate in Wallerian degeneration as well as in the reconstruction of nerve bridges and angiogenesis during axonal regeneration. Neutrophils appear early in the injury process and are primarily present at the injury site and the distal segment. After peripheral nervous system injury, immature neutrophils from the peripheral blood play a major role. Although lymphocytes constitute only a small fraction compared to macrophages and neutrophils after peripheral nervous system injury, they still play important roles, including Treg cells, B cells, and NK cells. A large number of immune cells accumulate at the injury site, contributing not only to Wallerian degeneration but also to axonal regeneration. Conclusion: In conclusion, this paper summarizes current knowledge regarding the mechanisms of immune cell infiltration after PNS injury, providing new insights for future research on the role of immune cells in peripheral nerve injury.