The immunomodulatory effect of Radix Astragali polysaccharides on experimental autoimmune encephalomyelitis by targeting the crosstalk between dendritic cells and Th17 cells

Background: Animal studies indicate that Radix Astragali polysaccharides (RAP) protect pancreatic β cells from T cell attack in type 1 diabetes, highlighting RAP's potential in autoimmune therapy. Besides, RAP controls tumor progression by modulating dendritic cell (DC) activity in breast tumor models. Multiple sclerosis (MS) is an autoimmune disease of the CNS characterized by demyelination due to autoreactive T cells. Experimental autoimmune encephalomyelitis (EAE) is induced in mice via myelin peptide immunization to recapitulate MS. This study investigates the therapeutic effects of RAP in EAE treatment and underlying mechanisms, particularly regarding DC. Methodology: C57BL/6 mice were immunized subcutaneously with MOG33-55 peptides and intraperitoneally with pertussis toxin to induce EAE. RAP or a vehicle control was administered orally daily from day 0 of immunization. Disease severity was scored on a scale of 0–5 based on paralysis extent. Brains and spinal cords were collected around 3 weeks post-immunization, minced, digested, and subjected to gradient centrifugation to isolate leukocytes, which then were restimulated and stained for cell surface markers and intracellular cytokines. DC were also isolated for RNA sequencing. Results and conclusion: In this study, RAP treatment significantly ameliorated the development of EAE and reduced Th17 infiltration and DC maturation in the CNS. Naïve T cells were less effective in polarizing into Th17 cells when treated with RAP. Additionally, the capacity of DC to induce naïve T cells into Th17 cells was impaired in mice treated with RAP following EAE immunization. RNA sequencing data revealed that RAP treatment downregulated the expression of vascular cell adhesion molecules, further confirming a reduction in the activation and antigen-presenting function of DC. Overall, this study indicates that RAP effectively controls the progression of EAE by targeting the crosstalk between Th17 cells and dendritic cells.