Trophoblast cells induce a tolerogenic profile in dendritic cells.
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-α, 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.
Immunology Department, Instituto de Investigaciones Hematológicas and Instituto de Estudios Oncológicos Fundación Maissa, Academia Nacional de Medicina, Buenos Aires, Argentina.
Gabriela
G
Salamone
Laura
L
Fraccaroli
Soledad
S
Gori
Esteban
E
Grasso
Daniel
D
Paparini
Jorge
J
Geffner
Claudia
C
Pérez Leirós
Rosanna
R
Ramhorst
D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D016650:Fluorescein-5-isothiocyanate; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D014327:Trophoblasts / Q000378:metabolism*; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016650:Fluorescein-5-isothiocyanate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007136:Immunoglobulins; D015847:Interleukin-4; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen