Adjuvant effect of a natural TLR4 ligand on dendritic cells (P4240)

Abstract

Defect of dendritic cell (DC) maturation in tumor microenvironments is an important immunological problem limiting the success of cancer immunotherapy. In this study, we investigated the immunostimulatory effect of a Mori fructus polysaccharide (MFP) on DCs, a type of potent antigen presenting cells. MFP induced phenotypic maturation of DCs, as proven by the elevated expression of CD40, CD80/86, and MHC-I/II molecules. MFP induced functional maturation of DCs, in that MFP increased the expression of IL-12, IL-1β, TNF-α, and IFN-β, decreased antigen capture capacity, and enhanced allogenic T cell stimulation. MFP efficiently induced maturation of normal toll-like receptor4 (TLR4) DCs from C57BL/6 and C3H/HeN mice, but not mutated TLR4 DCs from C3H/HeJ mice, suggesting that TLR4 might be one of the membrane receptors of MFP. We showed that MFP increased phosphorylation of mitogen-activated protein kinase (MAPKs), and nuclear translocation of NF-κB p65 subunit, which are signaling molecules downstream from TLR4. These results indicate that MFP induced DC maturation through TLR4 signaling.