Progesterone and VIP cross-talk enhances phagocytosis and anti-inflammatory profile in trophoblast-derived cells

- P4 enhanced the phagocytic function in trophoblast-derived cells.
- P4 and VIP modulated the balance of anti/pro-inflammatory mediators.
- P4 and VIP modulated transcription factor expression that could turn on tolerogenic programs.
- VPAC2 over-expression lead to enhanced phagocytosis mimicking P4-effect.
- P4-VIP network contribute to the homestasis and immune tolerance.

Trophoblast cells produce several inmmuneregulators like the Vasoactive Intestinal Peptide (VIP) and P4 targeting multiple circuits, and also display an intese phagocytic ability allowing embryo implantation in a tolerogenic context. Here, we explored whether P4 and VIP- crosstalk modulates trophoblast cell function, focus on the phagocytic ability and the immune homeostasis maintenance. P4 enhanced the phagocytosis in trophoblast-derived cells quantified by the engulfment of latex-beads or eryptotic erythrocytes. P4 and VIP modulated the balance of anti/pro-inflammatory mediators, increasing TGF-β expression, with no changes in IL-1, IL-6, or nitrites production. This modulation was accompained by transcription factor expression changes that could turn on tolerogenic programs represented by increased PPAR-γ and decreased IRF-5 expression. Finally, P4 stimulated VPAC2 expression in trophoblast cells and VPAC2 over-expression enhanced phagocytosis mimicking P4-effect. Therefore, P4 and VIP network enhances the phagocytic ability of trophoblast-derived cells, through a mechanism involving VPAC2 accompained with an anti-inflammatory context.