Dendritic Cells as a Novel Target for Erythropoietin: Studies in a Human System.

The immunomodulatory effects of erythropoietin (EPO) on the cellular and humoral compartments of the immune system have been described for some time; however, the mechanism of action by which EPO affects lymphocyte number and function has yet to be elucidated. Our search for possible mechanisms by which EPO affects these parameters led us to the novel discovery that EPO receptors (EPO-R) are expressed in dendritic cells (DCs), the most potent antigen presenting cells and most efficient T cell primers. Furthermore, we show that EPO has direct effects on the phenotype and function of human DCs. When added in vitro, EPO increased the percentage of peripheral blood originated DCs that express the co-stimulatory molecules CD80, CD86 and CD40. We also show that EPO up-regulates the level of expression of these molecules, as well as that of HLA-DR in monocyte-derived DCs. When added to immature DCs, EPO alone can induce their maturation. Furthermore, we demonstrate that EPO enhances DC function, as revealed by increased antigen uptake, secretion of interleukin (IL)-12 and stimulatory function in allogeneic mononuclear cell proliferation. We propose that DCs may represent a missing link which might explain previously observed immunomodulatory actions of EPO. Hence, our findings are of crucial importance and may open new clinical avenues for EPO in the optimization of ex-vivo DC-based vaccines, or when administered to patients in order to enhance immune system responses.