Regulatory T cells attenuate astrogliosis via IL-10/STAT3/PKC/vimentin signaling and promote neurological recovery after spinal cord injury.

Spinal cord injury (SCI) triggers reactive astrogliosis, leading to the formation of an astrocyte scar around the lesion. Regulatory T cells (Tregs), a subset of immune cells, infiltrate the peri-lesional area through the compromised blood-spinal cord barrier. However, the regulatory role of Tregs in post-SCI astrogliosis and its underlying mechanisms remain unclear. Here, we demonstrated that Tregs attenuate astrogliosis and promote neurological recovery after SCI. Treg-depleted mice exhibited exacerbated astrocyte activation, increased chondroitin sulfate proteoglycan (CSPG) deposition, and impaired axonal remodeling post-SCI. Through transcriptomic profiling, we identified vimentin (Vim) as a key gene in astrocytes upregulated by Treg depletion following SCI. In vitro Treg co-culture attenuated oxygen-glucose deprivation/reoxygenation (OGD/R)-induced astrocyte activation, CSPG secretion, and vimentin high expression. Virus-mediated vimentin knockdown recapitulated Treg-mediated suppression of in vitro astrocyte activation and in vivo astrogliosis, and further ameliorated Treg depletion-induced pathological outcomes. In vitro pharmacological studies in astrocytes reveal that vimentin expression is modulated by exogenous IL-10 signaling and downstream STAT3/PKC phosphorylation. These findings demonstrate that Tregs attenuate post-SCI astrogliosis via the IL-10/STAT3/PKC/vimentin signaling axis, thereby facilitating axonal remodeling and promoting neurological recovery. Our study provides novel insights into the Treg-mediated neuroimmune repair mechanisms and establishes promising therapeutic targets for SCI treatment.