Generation of dexamethasone and vitamin D3-treated human monocyte-derived dendritic cells with tolerogenic properties

Human monocyte-derived dendritic cells (DC) treated with dexamethasone and vitamin D3 (DexVitD3 DC) have tolerogenic properties and phenotype. DexVitD3 DC induce limited T-cell proliferation in an allogeneic mixed lymphocyte reaction and inhibit the T-cell proliferation induced by lipopolysaccharide and/or cytokine (TNFα/IL-1β) matured DC. Furthermore, T cells primed with DexVitD3 DC proliferate in response to restimulation with a distinct cytokine profile including significantly reduced production of IFNγ. DexVitD3 DC have characteristically low expression of the costimulatory molecules CD80/83/86 with high HLA-DR. Upon stimulation with lipopolysaccharide, DexVitD3 DC maintain their surface phenotype and produce large quantities of IL-10. We are currently characterising the cytokine profiles of DexVitD3 DC and the T cells they prime, as well as investigating whether these T cells have regulatory properties.

Cellular therapies are being explored as treatment for autoimmune diseases including rheumatoid arthritis. DexVitD3 DC have potential for future use in this field as well as being a useful tool to elucidate mechanisms of immune regulation.