Erythropoietin enhances immunostimulatory properties of immature dendritic cells

Summary Dendritic cells (DCs) are the most potent antigen‐presenting cells and play a crucial role by modulating the T cell immune response against infective agents, tumour antigens and alloantigens. The current study shows that differentiating bone marrow (BM)‐derived DCs but not fully differentiated DCs are targets of erythropoietin (EPO). Indeed, DCs emerging from rat bone marrow, but not splenic DCs, express the EPO receptor (Epo‐R) and respond to EPO stimulation displaying a more activated phenotype with increased CD86, CD40 and interleukin (IL)‐12 expression levels and a higher allostimulatory capacity on T cells than untreated DCs. Moreover, results here presented show that EPO up‐regulates Toll‐like receptor (TLR)‐4 in differentiating DCs rendering these cells more sensitive to stimulation by the TLR‐4 ligand lipopolysaccharide (LPS). Indeed, DCs treated with EPO and then stimulated by LPS were strongly allostimulatory and expressed CCR7, CD86, CD40, IL‐12 and IL‐23 at higher levels than those observed in DCs stimulated with LPS alone. It is tempting to speculate that EPO could act as an additional danger signal in concert with TLR‐4 engagement. Thus, EPO, beyond its erythropoietic and cytoprotective effects, turns out to be an immune modulator.