PMID- 22718280 OWN - NLM STAT- MEDLINE DCOM- 20130111 LR - 20231213 IS - 1460-2350 (Electronic) IS - 0268-1161 (Linking) VI - 27 IP - 9 DP - 2012 Sep TI - Trophoblast cells induce a tolerogenic profile in dendritic cells. PG - 2598-606 LID - 10.1093/humrep/des208 [doi] AB - BACKGROUND: Dendritic cells (DCs), which are biased toward a tolerogenic profile, play a pivotal role in tissue-remodeling processes and angiogenesis at the maternal-fetal interface. Here, we analyzed the effect of trophoblast cells on the functional profile of DCs to gain insight on the tolerogenic mechanisms underlying the human placental-maternal dialog at early stages of gestation. METHODS: DCs were differentiated from peripheral blood monocytes obtained from fertile women (n = 21), in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor during 5 days in culture. Then, DCs were cultured with trophoblast cells (Swan-71 cell line obtained from normal cytotrophoblast, at 7 weeks) for 24 h and for an additional 24 h in the absence or presence of lipopolysaccharide (LPS) from Escherichia coli. DCs were recovered and used for flow cytometry, enzyme-linked immunosorbent assay, RT-PCR and suppression and migration assays. RESULTS: Trophoblast cells significantly prevented the increase in CD83 expression induced by LPS without affecting the expression of CD86, CD40 and human leukocyte antigen-DR (P < 0.05). Trophoblast cells significantly decreased the production of IL-12p70 and tumor necrosis factor-alpha, while it increased the production of IL-10 (P < 0.05). No changes were observed in the production of IL-6 and monocyte chemotactic protein-1. The culture of DCs with trophoblast cells, also suppressed the stimulation of the allogeneic response triggered by LPS (P < 0.05). Conditioned DCs were able to increase the frequency of CD4 + CD25 + Foxp3 cells and this effect was accompanied by an increase in indoleamine 2, 3-dioxygenase expression in DCs (P < 0.05). CONCLUSIONS: The interaction of DCs with trophoblast cells promotes the differentiation of DCs into cells with a predominantly tolerogenic profile that could contribute to a tolerogenic microenvironment at the maternal-fetal interface. FAU - Salamone, Gabriela AU - Salamone G AD - Immunology Department, Instituto de Investigaciones Hematologicas and Instituto de Estudios Oncologicos Fundacion Maissa, Academia Nacional de Medicina, Buenos Aires, Argentina. FAU - Fraccaroli, Laura AU - Fraccaroli L FAU - Gori, Soledad AU - Gori S FAU - Grasso, Esteban AU - Grasso E FAU - Paparini, Daniel AU - Paparini D FAU - Geffner, Jorge AU - Geffner J FAU - Perez Leiros, Claudia AU - Perez Leiros C FAU - Ramhorst, Rosanna AU - Ramhorst R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120620 PL - England TA - Hum Reprod JT - Human reproduction (Oxford, England) JID - 8701199 RN - 0 (Antigens, CD) RN - 0 (B7-2 Antigen) RN - 0 (CD40 Antigens) RN - 0 (Immunoglobulins) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 207137-56-2 (Interleukin-4) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - I223NX31W9 (Fluorescein-5-isothiocyanate) SB - IM MH - Antigens, CD/biosynthesis MH - B7-2 Antigen/biosynthesis MH - CD40 Antigens/biosynthesis MH - Cell Differentiation MH - Cell Line MH - Cells, Cultured MH - Dendritic Cells/*cytology MH - Female MH - Flow Cytometry/methods MH - Fluorescein-5-isothiocyanate MH - *Gene Expression Regulation MH - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism MH - Humans MH - Immunoglobulins/biosynthesis MH - Interleukin-4/metabolism MH - Lipopolysaccharides/metabolism MH - Membrane Glycoproteins/biosynthesis MH - Models, Biological MH - Neovascularization, Pathologic MH - Trophoblasts/*metabolism MH - CD83 Antigen EDAT- 2012/06/22 06:00 MHDA- 2013/01/12 06:00 CRDT- 2012/06/22 06:00 PHST- 2012/06/22 06:00 [entrez] PHST- 2012/06/22 06:00 [pubmed] PHST- 2013/01/12 06:00 [medline] AID - des208 [pii] AID - 10.1093/humrep/des208 [doi] PST - ppublish SO - Hum Reprod. 2012 Sep;27(9):2598-606. doi: 10.1093/humrep/des208. Epub 2012 Jun 20.