Endothelial Cells in the Decidual Bed Are Potential Therapeutic Targets for Preterm Birth Prevention

Wenbo Deng; Jia Yuan; Jeeyeon Cha; Xiaofei Sun; Amanda Bartos; Hideo Yagita; Yasushi Hirota; Sudhansu K. Dey

Endothelial Cells in the Decidual Bed Are Potential Therapeutic Targets for Preterm Birth Prevention

2019

Summary: Preterm birth (PTB) is a syndrome with many origins. Among them, infection or inflammation are major risk factors for PTB; however, local defense mechanisms to mount anti-inflammatory responses against inflammation-induced PTB are poorly understood. Here, we show that endothelial TLR4 in the decidual bed is critical for sensing inflammation during pregnancy because mice with endothelial Tlr4 deletion are resistant to lipopolysaccharide (LPS)-induced PTB. Under inflammatory conditions, IL-6 is readily expressed in decidual endothelial cells with signal transducer and activator of transcription 3 (Stat3) phosphorylation in perivascular stromal cells, which then regulates expression of anti-inflammatory IL-10. Our observation that administration of an IL-10 neutralizing antibody predisposing mice to PTB shows IL-10’s anti-inflammatory role to prevent PTB. We show that the integration of endothelial and perivascular stromal signaling can determine pregnancy outcomes. These findings highlight a role for endothelial TLR4 in inflammation-induced PTB and may offer a potential therapeutic target to prevent PTB. : Deng et al. show a balance between inflammation and anti-inflammation involving endothelial and decidual cells in pregnancy. Tipping this balance toward inflammation contributes to preterm birth. A mechanism to preserve homeostatic balance in pregnancy under inflammation is mediated by a cross-talk between endothelial and perivascular stromal cells. Keywords: pregnancy, uterus, preterm birth, endothelial cell, decidua, TLR4, STAT3, LPS

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