IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Trophoblast cells induce a tolerogenic profile in dendritic cells
Autor/es:
SALAMONE G, FRACCAROLI L, GORI S, GRASSO E, PAPARINI D, GEFFNER J, LEIRÓS CP, RAMHORST R.
Revista:
HUMAN REPRODUCTION
Editorial:
OXFORD UNIV PRESS
Referencias:
Lugar: Oxford; Año: 2012 vol. 27 p. 2598 - 2606
ISSN:
0268-1161
Resumen:
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 ¼ 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 signifinatly decreased the production of IL-12p70 and tumor necrosis factor-a, 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.