The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their seminal discoveries identifying and characterizing the immune system’s key mediators of peripheral tolerance—regulatory T cells (Tregs). Tregs are now recognized as critical modulators of immune responses within the central nervous system (CNS), and therapeutic strategies centered on Tregs now represent a promising avenue for the treatment of a broad spectrum of neurological disorders. This highlight synthesizes the evolving understanding of the characteristics of brain Tregs, detailing their specialized immunosuppressive functions that maintain CNS homeostasis, their emerging neuroprotective roles across a spectrum of neurological conditions, and how Tregs show therapeutic potential in neuropsychiatric disorders, including neuroinflammatory, neurodegenerative, and neurodevelopmental disorders. We outline three primary approaches to harness Tregs to treat neurological disorders: increasing Treg numbers via adoptive transfer or low-dose IL-2 therapy; enhancing their specificity and function through genetic engineering; and developing combination strategies, such as co-culture with astrocytes or co-transplantation with neurons. Despite challenges in seeking balance between cell specificity and quantity and maintaining Treg function in inflammatory environments, recent advances underscore the significant potential of Treg-targeted therapies to revolutionize treatment for neuroinflammatory, neurodegenerative, and psychiatric diseases.
Gao et al. (Thu,) studied this question.