PMID- 21649646 OWN - NLM STAT- MEDLINE DCOM- 20110907 LR - 20211020 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 165 IP - 2 DP - 2011 Aug TI - Erythropoietin enhances immunostimulatory properties of immature dendritic cells. PG - 202-10 LID - 10.1111/j.1365-2249.2011.04417.x [doi] AB - 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. CI - (c) 2011 The Authors. Clinical and Experimental Immunology (c) 2011 British Society for Immunology. FAU - Rocchetta, F AU - Rocchetta F AD - Transplant Research Center Chiara Cucchi de Alessandri e Gilberto Crespi, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. FAU - Solini, S AU - Solini S FAU - Mister, M AU - Mister M FAU - Mele, C AU - Mele C FAU - Cassis, P AU - Cassis P FAU - Noris, M AU - Noris M FAU - Remuzzi, G AU - Remuzzi G FAU - Aiello, S AU - Aiello S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110607 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (B7-2 Antigen) RN - 0 (CD40 Antigens) RN - 0 (Ccr7 protein, rat) RN - 0 (Immunologic Factors) RN - 0 (Interleukin-23) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, CCR7) RN - 0 (Receptors, Erythropoietin) RN - 0 (Toll-Like Receptor 4) RN - 11096-26-7 (Erythropoietin) RN - 15UQ94PT4P (Darbepoetin alfa) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - B7-2 Antigen/biosynthesis MH - Blotting, Western MH - Bone Marrow Cells/metabolism MH - CD40 Antigens/biosynthesis MH - Cell Differentiation MH - Darbepoetin alfa MH - Dendritic Cells/*immunology/metabolism MH - Erythropoietin/*analogs & derivatives/immunology/metabolism/pharmacology MH - *Immunologic Factors/metabolism/pharmacology MH - Interleukin-12/biosynthesis MH - Interleukin-23/biosynthesis MH - Lipopolysaccharides/immunology MH - Polymerase Chain Reaction MH - Rats MH - Rats, Inbred BN MH - Receptors, CCR7/biosynthesis MH - Receptors, Erythropoietin/genetics/metabolism MH - Toll-Like Receptor 4/biosynthesis/genetics PMC - PMC3142645 EDAT- 2011/06/09 06:00 MHDA- 2011/09/08 06:00 PMCR- 2012/08/01 CRDT- 2011/06/09 06:00 PHST- 2011/06/09 06:00 [entrez] PHST- 2011/06/09 06:00 [pubmed] PHST- 2011/09/08 06:00 [medline] PHST- 2012/08/01 00:00 [pmc-release] AID - 10.1111/j.1365-2249.2011.04417.x [doi] PST - ppublish SO - Clin Exp Immunol. 2011 Aug;165(2):202-10. doi: 10.1111/j.1365-2249.2011.04417.x. Epub 2011 Jun 7.