In a healthy pregnancy, a finely tuned maternal immune response prevents the mother’s body from rejecting the growing fetus. But in some pregnancies, this response goes haywire, leading to a potentially dangerous complication known as chronic placental inflammation. To understand what drives this inflammation, researchers led by Nardhy Gomez-Lopez, PhD, a professor of obstetrics and gynecology and of pathology and immunology at WashU Medicine, used spatial and single-cell gene and protein expression profiling to map the immune cell landscape of the placenta in mothers who developed chronic placental inflammation, down to individual cells at the junction connecting the mother and fetus.
Their findings were published Oct. 7 in Science Translational Medicine.
Comparing tissue samples from mothers with the complication who delivered prematurely to those who carried to full term, the team discovered that the preterm cases involved an aggressive inflammatory reaction driven by immune cells from both mother and baby, including cytotoxic T cells, activated macrophages and natural killer cells. In contrast, when women with the condition carried to full term, the placenta had a more harmonious immune environment, with a high volume of cells that help heal tissue and keep inflammation under control.
The researchers also discovered that T cells in the placenta samples had receptors — specialized proteins on the cell surface that recognize foreign or abnormal substances — that mimicked receptors known to recognize common viruses such as influenza. This suggests that past viral infections might mistakenly spark inflammation in the placenta.
Together, the findings lay the groundwork for simple blood tests to spot early warning signs of premature birth and new treatments to safeguard high-risk pregnancies.