Suppressive effect of aqueous humor on lipopolysaccharide-induced dendritic cell maturation

Abstract

The aqueous humor (AH) contains numerous immunosuppressive molecules that contribute to the ocular immune privilege. Here, we mimic an inflammatory environment to analyze the inhibitory effects of the AH on lipopolysaccharide (LPS)-induced maturation of dendritic cells (DC). Different concentrations of AH were added to dendritic cell cultures together with LPS. Dendritic cell surface markers CD80, CD86, and MHC-II were assessed by use of flow cytometry. Endocytic capability and mixed lymphocyte reaction were measured as functional maturation. AH inhibited LPS-induced DC maturation, resulting in down-regulated expression of CD80, CD86, MHC-II, enhancement of endocytic capacity, and reduced T cell activation. Neutralizing transforming growth factor beta 2 (TGF-β(2)) in AH can totally reverse the inhibitory effect. Treatment with prostaglandin E2 (PGE(2)) antagonist alone had no effect on DC maturation. However, blocking of both TGF-β(2) and PGE(2) in the AH resulted in synergistic suppression of the inhibiting effect of AH. These results reveal that TGF-β(2) in the AH is of crucial importance in maintaining DC in the immature state. Further experiments will clarify the immune role of PGE(2) in AH.