Balancing inflammation and regeneration: immune cell dynamics in nerve repair: a comprehensive review

BACKGROUND: Nerve injuries initiate a complex immune response that is crucial for triggering repairprocesses but can also exacerbate tissue damage if dysregulated. A tightly regulated balancebetween pro-inflammatory and anti-inflammatory signals is essential for optimal nerveregeneration, as excessive or prolonged inflammation can impede repair, while insufficientimmune activation may delay debris clearance and regeneration. PURPOSE: This review aims to examine the roles of key immune cells, including macrophages,neutrophils, T cells, and B cells exert diverse roles in this process, orchestrating the inflammatoryenvironment and promoting tissue remodeling. Central to their function is metabolicreprogramming, which dictates immune cell activation, phenotype, and regenerative capacity. METHOD: Relevant literature on immune responses and metabolic regulation in nerve injury wasanalyzed to explore how shifts between glycolysis, oxidative phosphorylation, and fatty acidoxidation govern the balance between inflammatory and reparative states. Macrophages displayremarkable functional plasticity, transitioning from pro-inflammatory (M1-like) to proregenerative(M2-like) phenotypes in response to metabolic and microenvironmental cues.Emerging therapeutic strategies aim to harness this immune-metabolic plasticity to improveoutcomes after nerve injury. RESULTS: Evidence suggests that metabolic reprogramming is a critical determinant of immune cellbehavior in nerve repair. Interventions such as small-molecule modulators, metabolicglycoengineering, and targeted delivery systems are being explored to fine-tune immune cellmetabolism and restore inflammatory balance. However, challenges remain in achieving cell-typespecificity, managing the intricacies of the immune milieu, and ensuring safe and effective clinicaltranslation. This review examines the cellular and metabolic mechanisms underlying immunemediatednerve repair, highlights the critical importance of inflammatory balance in determiningregenerative outcomes, and discusses promising metabolic targets and therapeutic approaches. CONCLUSION: Understanding the interplay between immune responses and cellular metabolismoffers promising opportunities to enhance nerve regeneration. Advances in immunometabolismmay facilitate the development of precision therapeutic strategies aimed at optimizinginflammatory balance and improving functional recovery following nerve injury.