Abstract
BACKGROUND: Stroke remains a leading cause of mortality and disability among adults. Given the restricted therapeutic window for intravascular interventions and neuroprotection during the acute phase, there has been a growing focus on tissue repair and functional recovery in the subacute and chronic phases after stroke. The pro-inflammatory microglial polarization occurs in subacute and chronic phases after stroke and may represent therapeutic targets for stroke recovery. CD4(+) regulatory T cells (Tregs), a subtype of T cells with immunosuppressive effects, have been shown to be important in stroke. Tregs infiltrate into the brain primarily during the subacute and chronic phases following a stroke. Infiltrating Tregs play a critical role in mitigating pro-inflammatory microglial responses, modulating the immune microenvironment, and promoting the functional restoration of the damaged brain following a stroke. METHODS: A systematic literature search was conducted in PubMed, Scopus, and Web of Science and then conduct a comprehensive analysis of the searched literature. RESULTS: This review provides a comprehensive summary of recent preclinical research advances on the role of Tregs in stroke, with a particular focus on their reparative functions during the subacute and chronic phases. It discusses changes in peripheral and brain infiltrating Tregs post-stroke, their functions and underlying mechanisms, and therapeutic strategies involving Tregs. Additionally, this review explores the potential and challenges associated with the clinical application of Tregs in ischemic stroke. CONCLUSION: Treg cell-related therapy represents a promising immune-therapeutic strategy for stroke recovery. However, there are several critical issues that must be resolved before its advancement to clinical application.