Decidual natural killer cells regulate vessel stability: implications for impaired spiral artery remodelling

- dNK cells isolated from pregnancies with high or normal uterine artery resistance indices.
- Normal-RI dNK cells activate ECs and destabilise endothelial tube-like structures.
- Normal-RI dNK cells induce more TNFα production from ECs than high-RI dNK cells.
- TNFα destabilises endothelial tube-like structures.

Decidual NK (dNK) cells are present during uterine spiral artery remodelling, an event that is crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Spiral artery remodelling is impaired in the pregnancy complication pre-eclampsia. Although dNK cells are known to play active roles at the maternal-fetal interface, little is known about their effect on endothelial integrity, an important component of vessel stability. We present a study in which we have modelled dNK-endothelium interactions, using first-trimester dNK cells isolated from both normal pregnancies and those with impaired spiral artery remodelling. dNK cells were isolated from first-trimester pregnancies, screened by uterine artery Doppler ultrasound to determine resistance indices (RI) that relate to the extent of spiral artery remodelling. dNK culture supernatant from normal-RI pregnancies (but not high-RI pregnancies) destabilised endothelial tube-like structures in Matrigel, and normal-RI dNK cells induced endothelial intercellular adhesion molecule-1 and tumour necrosis factor-α expression to a greater extent than high-RI dNK cells. We have established a functional role for dNK cells in the disruption of endothelial structures and have suggested how impairment of this process may be contributing to the reduced vessel remodelling in pregnancies with a high uterine artery resistance index. These findings have implications for our understanding of the pathology of pre-eclampsia and other pregnancy disorders where remodelling is impaired.