Repopulated microglia promote regulatory T cell accumulation and spinal cord injury repair in mice

ABSTRACT: Spinal cord injury causes severe neurological dysfunction, largely driven by secondary injury processes, including neuroinflammation. As the resident immune cells of the central nervous system, microglia can rapidly repopulate throughout the central nervous system following depletion. Regulatory T cells, key mediators of inflammation resolution, also play important roles in tissue repair. However, whether microglial repopulation contributes to spinal cord injury repair and whether Tregs participate in this process remain unclear. Here, we established a microglial depletion-repopulation model using a colony-stimulating factor 1 receptor inhibitor and investigated the role of repopulated microglia in mice with spinal cord injury. Microglial repopulation significantly improved locomotor recovery, gait coordination, and bladder function after spinal cord injury. Histological assessments showed that microglial repopulation reduced lesion size, inhibited apoptosis, increased neuronal survival, and improved axonal integrity. Notably, microglial repopulation increased Treg accumulation and suppressed the release of proinflammatory factors in the injured spinal cord. Consistently, Treg depletion markedly attenuated the neuroprotective and functional benefits induced by microglial repopulation. These findings identify microglial depletion-repopulation as a potential experimental strategy for promoting repair after spinal cord injury.