PGE2 inhibits the proinfalmatory phenotipe induced by TGF-b on monocyte derived DC.

REMES LENICOV FEDERICO; VARESE AUGUSTO; MERLOTTI ANTONELA; GEFFNER JORGE; CEBALLOS ANA

Congreso; VI SLIMP/V LASRI; 2015

Prostaglandin E2 inhibits the proinflammatory phenotype induced by TGF-b on monocyte-derived dendritic cells Federico Remes Lenicov; Augusto Varese; Antonela Merlotti, Jorge Geffner ; Ana Ceballos Objectives Semen immunomodulatory properties are well recognized, but details are lacking regarding its effect on dendritic cells, the immune cells in charge of deciding the type of response against foreign antigens. Previously, we have demonstrated that seminal plasma prostaglandins (PG) induce a tolerogenic profile on monocyte-derived dendritic cells (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 the differentiation of DCs from monocytes. Methods Seminal plasma was obtained by centrifugation of semen samples donated by healthy volunteers. DCs were obtained by incubating peripheral blood monocytes (>85% purity) with GM-CSF and IL-4 for 5 days, in the absence (control) or presence of TGF-b (TGF-DCs), PGE2 (PG-DCs), the combination of these (TGF+PG-DCs) or seminal plasma (SP-DCs). DC phenotype and their ability to expand the CD4+CD25+FoxP3+ lymphocyte population was analyzed by flow cytometry. Cytokine production was measured by ELISA in cell culture supernatants. Results TGF-DCs showed a marked expression of CD1a and null expression of CD14. Addition of PGE2 (10-9 to 10-6 M) during differentiation of TGF-DCs reversed this phenotype, resulting in CD1a-CD14+ DCs, associated with tolerogenic properties and similar to that obtained for PG-DCs and SP-DCs. Moreover, stimulation of TGF-DCs with LPS resulted in increased production of IL-12p70 and IL-23 compared to control DCs, while TGF+PG-DCs were unable to produce IL-12p70 or IL-23 upon stimulation, as observed also for PG-DCs and SP-DCs. Finally, in a mixed-lymphocyte reaction, TGF-DCs suppressed the expansion of CD4+CD25+FoxP3+ cells compared to control DCs. In contrast, we observed increased expansion of this population comparing control DCs with TGF+PG-DCs, PG-DCs and SP-DCs. Conclusions The presence of PGE2 during differentiation abolishes the proinflammatory properties elicited by TGF-b in monocyte-derived DCs.