From pathogenesis to therapy: the emerging role of regulatory T cells in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons in the brain and spinal cord, with a pathogenesis that remains incompletely understood. Increasing evidence in recent years has highlighted the pivotal role of neuroinflammation in ALS, in which regulatory T cells (Tregs) emerge as key modulators of the neuroimmune response. This review systematically summarizes recent advances in understanding Treg biology in ALS, including their dynamic alterations across different disease stages and their potential immunoregulatory mechanisms, while also highlighting ongoing clinical trials and emerging cellular therapeutic strategies targeting Tregs. Current evidence suggests that Tregs not only participate in the immunopathology of ALS but also represent a promising target for therapeutic intervention. Nevertheless, there are still significant challenges, including incomplete mechanistic insights, limited clinical validation and obstacles to the implementation of Treg-based therapies. Overall, Treg research in ALS provides valuable directions for elucidating disease mechanisms and developing novel immune-based interventions.