Decidual factors and vasoactive intestinal peptide guide monocytes to higher migration, efferocytosis and wound healing in term human pregnancy

Abstract

Aim: To explore the functional profile of circulating monocytes and decidual macrophages at term human pregnancy and their contribution to tissue repair upon stimulation ex vivo with decidual factors and the vasoactive intestinal peptide (VIP). Methods: Peripheral blood monocytes were isolated from pregnant and non-pregnant volunteers and tested in vitro with decidual explants from term placenta and VIP. The effect of VIP on decidual explants and the effect of its conditioned media on monocytes or decidual macrophages isolated by magnetic beads was carried out by RT-qPCR and ELISA for cytokines expression and release. Migration assays were performed in transwell systems. Efferocytosis was assessed in monocytes or decidual macrophages with CFSE-labelled autologous apoptotic neutrophils and quantified by flow cytometry. Monocyte and decidual macrophages wound healing capacity was evaluated using human endometrial stromal cell monolayers. Immunohistochemistry was performed in serial tissue sections of different placentas. Results: VIP is expressed in the villi as well as in trophoblast giant cells distributed within the decidua of term placenta. VIP induced the expression of antiinflmammatory markers and monocyte chemoattractant CCL2 and CCL3 in decidual tissues. Monocytes presented higher migration towards decidual explants than CD4 and CD8 cells. VIP-conditioned monocytes displayed an enhanced efferocytosis and wound healing capacity comparable to that of decidual macrophages. Moreover limited efferocytosis of pregnant women monocytes was restored by VIP-induced decidual factors. Conclusion: Results show the conditioning of monocytes by decidual factors and VIP to sustain processes required for tissue repair and homeostasis maintenance in term placenta.

VIP: The big shot peptide in pregnancy and beyond?

“…Underneath this, resides the villous stroma and foetal vasculature. Paparini et al 2 myometrium. The EVT persist within the uterus as gestation progresses, alongside trophoblast giant cells.…”

“…1 In this issue of Acta Physiologica, Paparini et al have explored the roles of monocytes, macrophages and vasointestinal peptide (VIP) in uterine tissue repair and homeostasis. 2 Establishment of a functional interface between the foetal-derived placenta and maternal uterine decidua is critical for pregnancy success. During the secretory phase of the menstrual cycle, under the influence of progesterone, the uterine endometrium becomes hypertrophic and increases in vascularity in preparation for implantation.…”

“…10 In this manuscript, they explore how placentalderived VIP can influence both the behaviour of the decidua and decidual immune cell populations, to maintain tissue homeostasis at the maternofoetal interface. 2 The human placenta is a uniquely structured organ, composed of microscopic finger-like projections called villi, which are organised into villous trees. 11 Each villus is covered by a bilayer of placental trophoblast cells, which consists of the maternal-facing syncytiotrophoblast, a multinucleated single cell compartment, overlying a proliferative layer of cytotrophoblast.…”

“…Complex immune dialogues take place within the endometrium prior to pregnancy, at the site of implantation to facilitate placental development and establishment of the maternofoetal interface, and throughout gestation to maintain local tissue architecture and function 1 . In this issue of Acta Physiologica, Paparini et al have explored the roles of monocytes, macrophages and vasointestinal peptide (VIP) in uterine tissue repair and homeostasis 2 …”

“…Since then, the Ramhorst and Pérez Leirós labs have produced a large body of work in this area, and have demonstrated the critical effects of VIP on the placenta, neutrophils, regulatory T cells, peripheral blood monocytes and macrophages; at implantation, during placental development and throughout gestation 10 . In this manuscript, they explore how placental‐derived VIP can influence both the behaviour of the decidua and decidual immune cell populations, to maintain tissue homeostasis at the maternofoetal interface 2 …”