Natural killer cells are part of the body's defense system, ruthless destroyers of invading armies of bacteria or viruses. Yet in the first trimester of pregnancy they show another side, gentle and nurturing. Far from attacking the fetus as a foreign object, as the immune system can sometimes do, they ensure it gets the nutrients it needs to grow. The team that discovered this trait have taken the first steps to harnessing it to combat nutrient starvation of the fetus.
Over our evolutionary history many cell types have taken on multiple roles, often ones that seem quite incongruous with their original capacities. The presence of large numbers of natural killer cells early in pregnancy alerted scientists long ago to an example of this flexibility, but the extent of the role was unknown.
Professor Haiming Wei of the University of Science and Technology of China has helped to clarify this, publishing his study in the journal Immunity, showing that a subgroup of natural killer cells in the uterine lining make a specific contribution. Importantly, a shortage of these cells is associated with miscarriage.
This group, known as CD49a+Eomes+ cells, secrete pleiotrophin and osteoglycin, both of which are proteins that promote growth and encourage the early development of the fetus.
Among a group of women who experienced healthy pregnancies, CD49a+Eomes+ represented more than 81 percent of the natural killer cells in the uterine lining. On the other hand, for women who suffered repeated miscarriages, they represented just 42 percent.
When Wei looked at mice with a similar shortage of CD49a+Eomes+ cells, the growth factors were found to also be low, which in turn led to severe fetal growth restrictions and failure of the skeleton to develop normally.
Wei then transferred CD49a+Eomes+ cells to mice with a natural deficiency. Increased growth factors were produced and deficiencies in fetal growth reversed. CD49a+Eomes+ rates are lower in older mice, likely to be a factor in lower rates of successful pregnancies as women age.
The ultimate goal of preventing miscarriages and growth deficiencies in humans remains a long way off. One important step forward, however, is to explain how the growth-promoting factors work their magic. At this stage it is unclear if they operate directly within the fetus, or if they stay within the mother, but stimulate the growth of the placenta and blood vessels that feed the fetus the nutrients it needs. Nevertheless, the paper notes the transfer of CD49a+Eomes+ cells, potentially sourced from umbilical cord cells, should be much less risky than using pluripotent stem cells, an alternative that could have similar stimulatory effects.
After the placenta forms, CD49a+Eomes+ cell numbers decline significantly, apparently having fulfilled their nurturing role, and only being needed for protection thereafter.
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