PROSTAGLANDIN E2 INHIBITS THE PROINFLAMMATORY PHENOTYPE INDUCED BY TGF-b ON MONOCYTE-DERIVED DENDRITIC CELLS

F. REMES LENICOV; A. VARESE; A. MERLOTTI; J. GEFFNER; A. CEBALLOS

Mar del Plata

Congreso; V Latin American Symposium on Reproductive Immunology; 2015

Latin American Society on Reproductive Immunology

Objectives: The immunomodulatory properties of semen are well recognized,but details are lacking regarding its effect on dendritic cells, theimmune cells in charge of deciding the type of response against foreignantigens. Previously, we have demonstrated that seminal plasma prostaglandins(PG) induce a tolerogenic profile on monocyte-derived dendriticcells (DCs). Human seminal plasma also contains high amounts of TGF-b,which has been shown to promote a proinflammatory phenotype in DCs.We aim to characterize the interaction between PG and TGF-b during thedifferentiation of DCs from monocytes.Methods: Seminal plasma was obtained by centrifugation of semensamples donated by healthy volunteers. DCs were obtained by incubatingperipheral blood monocytes (>85% purity) with GM-CSF and IL-4 for 5days, in the absence (control) or presence of TGF-b (TGF-DCs), PGE2 (PGDCs),the combination of these (TGF+PG-DCs) or seminal plasma (SP-DCs).DCs and their ability to expand the CD4+CD25+FoxP3+ lymphocyte populationwas analyzed by flow cytometry. Cytokine production wasmeasured by ELISA in cell culture supernatants.Results: TGF-DCs showed a marked expression of CD1a and null expressionof CD14. Addition of PGE2 (10-9 to 10-6 M) during differentiation ofTGF-DCs reversed this phenotype, resulting in CD1a-CD14+ DCs, associatedwith tolerogenic properties and similar to that obtained for PG-DCs andSP-DCs. Moreover, stimulation of TGF-DCs with LPS resulted in increasedproduction of IL-12p70 and IL-23 compared to control DCs, while TGF+PGDCswere unable to produce IL-12p70 or IL-23 upon stimulation, asobserved also for PG-DCs and SP-DCs. Finally, in a mixed-lymphocyte reaction, TGF-DCs suppressed the expansion of CD4+CD25+FoxP3+ cellscompared to control DCs. In contrast, we observed increased expansion ofthis population comparing control DCs with TGF+PG-DCs, PG-DCs and SPDCs.Conclusions: The presence of PGE2 during differentiation abolishes theproinflammatory properties elicited by TGF-b in monocyte-derived DCs.