Neuroimmune interactions: How past lessons can inform the present and future of MS care

The recognized spectrum of neuroimmune interactions has expanded significantly, with increasing relevance to the pathogenesis and course of multiple sclerosis (MS). This review examines the bidirectional nature of these interactions-how systemic immune activity can initiate or modulate central nervous system (CNS) pathology, and how CNS-derived signals may shape peripheral immune responses. Particular attention is given to lesion compartmentalization, the impact of aging and comorbidity, and the dual roles of glial and immune cells in injury and repair. By integrating recent findings from experimental models and clinical observations, we consider how these principles inform evolving therapeutic approaches in MS and related disorders. This present overview was presented in part as the Kenneth P. Johnson Memorial Presidential Lecture at the ACTRIMS Forum 2025.