From a mother's perspective, a fetus is a bag full of foreign antigens—invaders against which an immune system might be expected to protect. But, according to Jacob Hanna, Ofer Mandelboim (Hebrew University, Jerusalem, Israel), and colleagues, certain immune cells actually help fetal cells to invade the uterus and ensure an adequate blood supply. Their success is essential to avoid the often fatal condition of preeclampsia.

All this cellular action takes place in the decidua, the outer lining of the uterus during pregnancy. Up to 40% of the cells in this tissue are maternal natural killer (NK) cells—but specifically the NK cells rich in CD56. Unlike the majority of circulating NK cells, these dNK cells are good at excreting proinflammatory cytokines and bad at killing infected cells.

The Israeli group found that dNK cells produce chemokines that can attract embryonic cells called trophoblasts. These trophoblasts form the placenta, in part by invading the decidua and tapping into the underlying blood vessels. Blood vessel growth and remodelling appears to be further aided by the VEGF now found to be secreted by dNK cells.

If this invasion is insufficient, the result is preeclampsia: blood vessels that do not fully penetrate the myometrium result in high blood pressure in the mother and fetus, which can only be relieved by delivering the fetus. In a recent genetic study, preeclampsia risk was greatest for parental gene combinations that inhibited dNK cell activation. Thus, when fetal cells are looking for a foothold, a pacifist subset of killer cells is the critical collaborator.


Hanna, J., et al.
Nat. Med.