Transcriptomics and Immunological Analyses Reveal a Pro-Angiogenic and Anti-Inflammatory Phenotype for Decidual Endothelial Cells.

Chiara Agostinis,Fleur Bossi,Valter Gattei,Elisa Masat,Giuseppe Ricci,Uday Kishore,Marie-Pierre Piccinni,Gabriella Zito,Alessandro Mangogna,Letizia Lombardelli,Renzo Menegazzi,Roberta Bulla,Massimo Degan

doi:10.3390/ijms20071604

Abstract

Background: In pregnancy, excessive inflammation and break down of immunologic tolerance can contribute to miscarriage. Endothelial cells (ECs) are able to orchestrate the inflammatory processes by secreting pro-inflammatory mediators and bactericidal factors by modulating leakiness and leukocyte trafficking, via the expression of adhesion molecules and chemokines. The aim of this study was to analyse the differences in the phenotype between microvascular ECs isolated from decidua (DECs) and ECs isolated from human skin (ADMECs). Methods: DECs and ADMECs were characterized for their basal expression of angiogenic factors and adhesion molecules. A range of immunological responses was evaluated, such as vessel leakage, reactive oxygen species (ROS) production in response to TNF-α stimulation, adhesion molecules expression and leukocyte migration in response to TNF-α and IFN-γ stimulation. Results: DECs produced higher levels of HGF, VEGF-A and IGFBP3 compared to ADMECs. DECs expressed adhesion molecules, ICAM-2 and ICAM-3, and a mild response to TNF-α was observed. Finally, DECs produced high levels of CXCL9/MIG and CXCL10/IP-10 in response to IFN-γ and selectively recruited Treg lymphocytes. Conclusion: DEC phenotype differs considerably from that of ADMECs, suggesting that DECs may play an active role in the control of immune response and angiogenesis at the foetal-maternal interface.

Highlights

Endothelial cells (ECs) form a continuous barrier between blood and tissues and act as a gateway to the traffic of molecules and cells across the vessel wall, playing an active role in homeostasis, inflammation and immunity [1]
The aim of this study was to analyse the differences in the phenotype between microvascular ECs isolated from decidua (DECs) and ECs isolated from human skin (ADMECs)
Decidual endothelial cells (DECs) differ from Adult Dermal Microvascular ECs (ADMECs) with respect to the production of several growth factors that play important roles in the control of angiogenesis

Summary

Introduction

Endothelial cells (ECs) form a continuous barrier between blood and tissues and act as a gateway to the traffic of molecules and cells across the vessel wall, playing an active role in homeostasis, inflammation and immunity [1]. Dermal microvascular ECs are active regulators of the inflammatory process [5] They contribute to the secretion of inflammatory mediators, bactericidal molecules, increasing leakiness and pro-coagulant activity, modulation of adhesion and transmigration of leukocytes through the expression of adhesion molecules and chemokines [6]. Endothelial cells (ECs) are able to orchestrate the inflammatory processes by secreting pro-inflammatory mediators and bactericidal factors by modulating leakiness and leukocyte trafficking, via the expression of adhesion molecules and chemokines. Conclusion: DEC phenotype differs considerably from that of ADMECs, suggesting that DECs may play an active role in the control of immune response and angiogenesis at the foetal-maternal interface

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