The neuro‐immune interface in multiple sclerosis: From pathogenesis to therapeutic opportunities

Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system, characterized by demyelination and axonal damage. The epidemiology of MS reflects a complex interplay between genetic susceptibility, including specific HLA alleles, and environmental factors such as geographic location, vitamin D status, and Epstein‐Barr virus infection. MS is more common in women, who more frequently develop relapsing‐remitting disease, whereas primary progressive MS is relatively more common in men. Disruption of the blood‐brain barrier facilitates immune‐cell infiltration and promotes neuroinflammation. The innate immune response involves macrophages, microglia, and other cell types that contribute to inflammation and neuronal damage. In contrast, the adaptive immune response is driven by autoreactive T and B cells, which damage myelin and neurons through cytokine production and antigen presentation. Glial cells play context‐dependent roles in both promoting neuroinflammation and supporting tissue repair. Key molecular mechanisms include MHC‐mediated antigen presentation, complex networks of pro‐inflammatory and anti‐inflammatory cytokines and chemokines that regulate cell migration, colony‐stimulating factors, and complement system activation. Current therapeutic approaches primarily emphasize immunomodulation and immunosuppression using agents such as interferon‐β, glatiramer acetate, monoclonal antibodies, and inhibitors of cell migration. Recent therapeutic developments, including cellular therapies and strategies that modulate the gut microbiota, offer new avenues for improving disease control and promoting repair in MS. Despite these advances, the interactions among immune, glial, and molecular mechanisms remain incompletely understood. Defining these interactions more precisely will be essential for developing more targeted and effective therapies.