title: Erythropoietin enhances immunostimulatory properties of immature dendritic cells.
abstract: 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.
authors.affiliation: Transplant Research Center Chiara Cucchi de Alessandri e Gilberto Crespi, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rocchetta
authors.forename: S
authors.initials: S
authors.lastname: Solini
authors.forename: M
authors.initials: M
authors.lastname: Mister
authors.forename: C
authors.initials: C
authors.lastname: Mele
authors.forename: P
authors.initials: P
authors.lastname: Cassis
authors.forename: M
authors.initials: M
authors.lastname: Noris
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
authors.forename: S
authors.initials: S
authors.lastname: Aiello
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D000068256:Darbepoetin alfa; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D007155:Immunologic Factors / Q000378:metabolism / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D016133:Polymerase Chain Reaction; D051381:Rats; D011914:Rats, Inbred BN; D054400:Receptors, CCR7 / Q000096:biosynthesis; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; C515372:Ccr7 protein, rat; D007155:Immunologic Factors; D053759:Interleukin-23; D008070:Lipopolysaccharides; D054400:Receptors, CCR7; D017467:Receptors, Erythropoietin; D051197:Toll-Like Receptor 4; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D018664:Interleukin-12