Control of the inflammatory response during pregnancy: potential role of VIP as a regulatory peptide

Abstract

A network of cell-cell communications through contact and soluble factors supports the maternal-placental interaction and provides a suitable environment for fetal growth. Trophoblast cells take center stage at these loops: they interact with maternal leukocytes to sustain the varying demands of gestation, and they synthesize hormones, cytokines among other factors that contribute to the maintenance of immune homeostasis. Here, we discuss vasoactive intestinal peptide (VIP) and its potential as a regulatory neuropeptide in pregnancy. VIP is synthesized by trophoblast cells; it regulates trophoblast cell function and interaction with the major immune cell populations present in the pregnant uterus. VIP activity produces an anti-inflammatory microenvironment by modulating the functional profile of monocytes, macrophages, and regulatory T cells. Trophoblast VIP inhibits neutrophil extracellular trap formation and accelerates neutrophil apoptosis, enabling their silent clearance by phagocytic cells. The effects of VIP on the trophoblast-immune interaction are consistent with its regulatory role throughout pregnancy for immune homeostasis maintenance. These observations may provide new clues for pharmacological targeting of pregnancy complications associated with exacerbated inflammation.

The role of neutrophil activation in determining the outcome of pregnancy and modulation by hormones and/or cytokines

“…Originally described as a neuropeptide, VIP has emerged as a very interesting regulatory factor at the feto-maternal interface [27,81]. In human pregnancy, VIP is expressed by the syncytiotrophoblast directly at the site of fetomaternal interaction, highly suggestive of a crucial role in regulating the maternal immune response [81].…”

“…While an essential function of these hormones is to regulate maternal metabolism in order to promote fetal growth or alter the ability of fetal trophoblast cells to invade maternal tissue, several of these factors have been shown to possess additional immune modulatory capacity [25,26]. hCG is produced by the syncytiotrophoblast, the single layer of contiguous fetal tissue directly in contact with the maternal circulation, while VIP is produced by the underlying cytotrophoblast tissue [27]. hCG is produced by the syncytiotrophoblast, the single layer of contiguous fetal tissue directly in contact with the maternal circulation, while VIP is produced by the underlying cytotrophoblast tissue [27].…”

“…Of particular interest in this discourse is human chorionic gonadotrophin (hCG) and vasoactive intestinal peptide (VIP) [27]. hCG is produced by the syncytiotrophoblast, the single layer of contiguous fetal tissue directly in contact with the maternal circulation, while VIP is produced by the underlying cytotrophoblast tissue [27]. As discussed below, both exhibit the ability to modify PMN behaviour during pregnancy.…”

“…© 2019 British Society for Immunology, Clinical and Experimental Immunology, 198:[24][25][26][27][28][29][30][31][32][33][34][35][36] …”

VIP Promotes Recruitment of Tregs to the Uterine–Placental Interface During the Peri-Implantation Period to Sustain a Tolerogenic Microenvironment

“…It has been extensively demonstrated that endometrial and trophoblastic cells contribute to the maintenance of immune homeostasis through soluble and contact factors during pregnancy (3,(14)(15)(16)(17). One of the factors proposed to have an immunoregulatory role during implantation and at the early maternal-fetal interface is vasoactive intestinal peptide (VIP) (18,19). VIP is produced by stromal cells (20), syncytium, and cytotrophoblastic cells in the first and third trimesters (21) by extravillous trophoblast (EVT) cells and decidual glandular cells (22,23).…”