Endothelial Cells in the Decidual Bed Is a Potential Target for Preterm Birth

Abstract

Preterm birth (PTB) is a syndrome with many origins. Among them, infection/inflammation are increased risk factors for PTB. Local defense mechanisms to mount anti-inflammatory responses against inflammation-induced PTB is poorly understood. Here we show that endothelial TLR4 in the decidual bed is critical for sensing inflammation, since mice with endothelial Tlr4 deletion are resistant to LPS-induced PTB. Under inflammation, IL6 is readily expressed in decidual endothelial cells with Stat3 phosphorylation in perivascular decidual cells which transcriptionally regulates expression of anti-inflammatory IL10. Our observation that administration of IL10-neutralizing antibody makes mice predisposed to PTB is consistent with IL10’s role as anti-inflammatory. This integration of endothelial-perivascular stromal signaling that determines pregnancy outcomes provide evidence for a previously unappreciated role of endothelial TLR4 in pregnancy. These findings provide novel insights into inflammation-induced PTB with high relevance to human pregnancy and may offer a new strategy to prevent PTB.