Potential immunomodulatory role of VIP in the implantation sites of prediabetic NOD mice

ROCA V; CALAFAT M; LAROCCA L; RAMHORST R; FARINA M; FRANCHI A; PÉREZ LEIRÓS C

REPRODUCTION

BioScientifica

Año: 2009 vol. 138 p. 733 - 742

1470-1626

Among several factors known to modulate embryo implantation and survival, uterine quiescence and neovascularization, maternal immunotolerance through the Th1/Th2 cytokine balance towards a Th2 profile, local regulatory T cell activation and high levels of progesterone were assigned a prominent role. Vasoactive intestinal peptide (VIP) is a neuroimmunopeptide that has anti-inflammatory effects, promotes Th2 cytokines and CD4+CD25+Foxp3+ regulatory T cell activation whereas it stimulates exocrine secretion, smooth muscle relaxation and vasodilatation favoring uterus quiescence. The goal of the present work was to explore the participation of VIP in the implantation sites of normal and pregnant prediabetic NOD females, a mouse strain that spontaneously develops an autoimmune exocrinopathy similar to Sjögren’s syndrome. Our results indicate a reduction in litter size from the 3rd parturition onwards in the NOD female lifespan with increased resorption rates. Progesterone systemic levels were significantly decreased in pregnant NOD mice compared with BALB/c mice, although the allogeneic response to progesterone by spleen cells was not impaired. VIP receptors VPAC1 and VPAC2 were expressed at the implantation sites and VIP induced LIF and Treg marker expression in both strains, however, a reduced VIP expression was found in NOD implantation sites. We conclude that the reduced birth rate at 16 week-old NOD mice with a Th1 systemic cytokine profile involves resorption processes with a lower expression of VIP at the sites of implantation which acts as a local inducer of pro-implantatory LIF and regulatory T cell activation.