CD8+T cell infiltration-associated barrier function of brain endothelial cells is enhanced by astragalus polysaccharides via inhibiting the PI3K/AKT signaling pathway.

Pathogenic CD8+T cells play an essential role in neuroinflammation and neural injury, which leads to the progression of inflammatory neurological disorders. Thus, blocking the infiltration of CD8+T cells is necessary for the treatment of neuroinflammatory diseases. Our previous study demonstrated that astragalus polysaccharide (APS) could significantly reduce the infiltration of CD8+T cells in experimental autoimmune encephalomyelitis mice. However, the mechanism by which APS suppresses CD8+T cell infiltration remains elusive. In this study, we further found that APS could reduce the CD8+T cell infiltration in experimental autoimmune encephalomyelitis and lipopolysaccharide (LPS)-induced neuroinflammatory model. Furthermore, we established the mouse brain endothelial cell (bEnd.3) inflammatory injury model by interleukin-1β or LPS in vitro. The results showed that APS treatment downregulated the expression of vascular cell adhesion molecule1 to decrease the adhesion of CD8+T cells to bEnd.3 cells. APS also upregulated the expression of zonula occludens-1 and vascular endothelial cadherin to reduce the transendothelial migration of CD8+T cells. The PI3K/AKT signaling pathway might mediate this protective effect of APS on bEnd.3 cells against inflammatory injury. In addition, we demonstrated the protective effect of APS on the integrity of brain endothelial cells in an LPS-induced neuroinflammatory model. In summary, our results indicate that APS can reduce peripheral CD8+T cell infiltration via enhancing the barrier function of brain endothelial cells; it may be a potential for the prevention of neuroinflammatory diseases.