IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
artículos
Título:
VIP boosts regulatory T cell induction by trophoblast cells in an in vitro model of trophoblast-maternal leukocyte interaction
Autor/es:
FRACCAROLI L; GRASSO E; HAUK V; PAPARINI D; MOR G; PEREZ LEIROS C; RAMHORST R
Revista:
JOURNAL OF LEUKOCYTE BIOLOGY
Editorial:
FEDERATION AMER SOC EXP BIOL
Referencias:
Lugar: Bethesda; Año: 2015 vol. 98 p. 49 - 58
ISSN:
0741-5400
Resumen:
Inducible regulatory T cells (iTreg) exert a timely and efficient immunosuppressive action at the critical peri-implantation stage essential for maternal tolerance to the conceptus. Vasoactive intestinal peptide (VIP) promotes anti-inflammatory and tolerogenic profiles through binding to VPAC receptors on immune cells. We evaluated whether VIP produced by trophoblast cells induces Treg cells during the early interaction of maternal leukocytes with trophoblast cells thus contributing to maternal tolerance. We used an in vitro model of maternal leukocyte-trophoblast cell interaction represented by co-cultures of fertile women?s PBMC with human trophoblast cell line (Swan-71) and evaluated the effect of VIP added exogenously and of the endogenous polypeptide. VIP increased the frequency of CD4+CD25+FoxP3+ cells after co-culture and these cells were able to suppress the maternal alloresponse. VIP also increased the frequency of CD4+IL10+ and CD4+TGF+ cells while it did not modulate IFN or IL-17 production. Interestingly, Swan-71 secreted VIP and their co-culture with maternal PBMC significantly increased the frequency of Treg. This effect was even more pronounced if trophoblast cells were pre-treated with VIP. In both situations VIP antagonist prevented the increase in the frequency of CD4+Foxp3+ cells, reflecting a specific effect of the polypeptide after the interaction with Swan-71 cells. Finally, the increase in CD4+CD25+FoxP3+ frequency was prevented by an anti TGFb Ab and VIP antagonist. These results suggest that VIP could have an active role in the immunoregulatory processes operating in the maternal-placental interface by contributing to the induction of Treg through a mechanism involving TGFb1.