The Role of Different Lymphoid Cell Populations in Preeclampsia Pathophysiology

Abstract

Preeclampsia (PE), new-onset hypertension during pregnancy, affects up to 10% of pregnancies worldwide. Despite being the leading cause of maternal and fetal morbidity and mortality, there is no cure for PE beyond the delivery of the fetal-placental unit. Although the exact pathogenesis of PE is unclear, there is a strong correlation between chronic immune activation, intrauterine growth restriction, uterine artery resistance, dysregulation of the renin angiotensin system which contributes to renal dysfunction, and the resulting hypertension during pregnancy. The genesis of PE is thought to begin with insufficient trophoblast invasion leading to reduced spiral artery remodeling resulting in decreased placental perfusion thereby causing placental ischemia. The ischemic placenta releases factors that shower the endothelium and contribute to peripheral vasoconstriction and chronic immune activation and oxidative stress. Studies have shown imbalances in pro-inflammatory and anti-inflammatory cell types in women with PE and in animal models utilized to examine mediators of a PE phenotype during pregnancy. T cells, B cells, and natural killer cells have all emerged as potential mediators contributing to the production of vasoactive factors, renal and endothelial dysfunction, mitochondrial dysfunction, and hypertension during pregnancy. The chronic immune activation seen in PE leads to a higher risk for other diseases such as cardiovascular disease, chronic kidney disease, dementia during their postpartum period, and PE during a subsequent pregnancy. The purpose of this review is to highlight studies demonstrating the role that different lymphoid cell populations play in the pathophysiology of PE. Moreover, we will discuss treatments focused on restoring immune balance or targeting specific immune mediators that may be potential strategies to improve maternal and fetal outcomes associated with PE.

Hypertension in Pregnancy: What We Now Know

“…Normal pregnancy ensures maternal tolerance to fetal alloantigens by shifting towards the delicate balance between TH1 and TH2 cells towards TH2 cells. Preeclampsia, however, sees a predominance of TH1 cells and their associated inflammatory cytokines [68 ▪ ,69 ▪ ], which likely contributes to poor placentation and endothelial dysfunction. Further, the alternative complement pathway is activated in preeclampsia as its byproduct.…”