Harnessing Regulatory T Cells to Modulate Acute Brain Injury: From Mechanisms to Therapy.

Neuroinflammation is a defining feature of acute brain injury such as acute ischemic stroke, traumatic brain injury, intracerebral hemorrhage, and subarachnoid hemorrhage, driven by complex immune interactions within the central nervous system (CNS). Among these, regulatory T cells (Tregs) have emerged as pivotal modulators that counteract the deleterious effects of effector T cell subsets, including Th1 and Th17 cells, which exacerbate blood-brain barrier (BBB) disruption, leukocyte infiltration, and glial activation. In contrast, Tregs exert immunosuppressive and tissue-reparative effects that promote neuroprotection, BBB integrity, and resolution of inflammation. This review examines the mechanistic roles of Tregs in modulating CNS-resident cells such as microglia, astrocytes, and endothelial cells, with emphasis on their capacity to suppress inflammation and support functional recovery. We also highlight emerging therapeutic strategies including low-dose interleukin-2 for selective Treg expansion, exosome-based immunomodulation, and chemokine-directed cell trafficking as promising avenues for clinical intervention. Finally, we discuss translational efforts to harness Tregs in acute neuroinflammatory disease, highlighting their potential as key targets for future therapies.