Macrophage roles in peripheral nervous system injury and pathology: Allies in neuromuscular junction recovery

• Published in: Molecular and cellular neuroscience 2021-03, Vol.111, p.103590-103590, Article 103590
• Main Authors: Rios, Rachel, Jablonka-Shariff, Albina, Broberg, Curtis, Snyder-Warwick, Alison K.
• Format: Article
• Language: English
• Subjects: Animals; Glial cells; Humans; Macrophage; Macrophages - immunology; Motor Neuron Disease - immunology; Motor Neuron Disease - physiopathology; Nerve injury; Nerve Regeneration; Neuromuscular junction; Neuromuscular Junction - immunology; Neuromuscular Junction - physiology; Neuromuscular Junction - physiopathology; Peripheral Nerve Injuries - immunology; Peripheral Nerve Injuries - physiopathology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2021.103590

Peripheral nerve injuries remain challenging to treat despite extensive research on reparative processes at the injury site. Recent studies have emphasized the importance of immune cells, particularly macrophages, in recovery from nerve injury. Macrophage plasticity enables numerous functions at the injury site. At early time points, macrophages perform inflammatory functions, but at later time points, they adopt pro-regenerative phenotypes to support nerve regeneration. Research has largely been limited, however, to the injury site. The neuromuscular junction (NMJ), the synapse between the nerve terminal and end target muscle, has received comparatively less attention, despite the importance of NMJ reinnervation for motor recovery. Macrophages are present at the NMJ following nerve injury. Moreover, in denervating diseases, such as amyotrophic lateral sclerosis (ALS), macrophages may also play beneficial roles at the NMJ. Evidence of positive macrophages roles at the injury site after peripheral nerve injury and at the NMJ in denervating pathologies suggest that macrophages may promote NMJ reinnervation. In this review, we discuss the intersection of nerve injury and immunity, with a focus on macrophages. •Macrophages are essential to nerve regeneration after injury or in denervating disease.•Different macrophage phenotypes contribute to nerve degeneration and regeneration, distinguished by differential growth factor expression.•Macrophages likely play a significant role at the NMJ, and therefore are good candidates for future research.•A more complete understanding of the interplay between the immune system and nerve repair may allow new treatments and enhance muscle recovery.