Embryonic development requires the formation of a special maternal-fetal interface to protect the normal development of the fetus. In the first trimester of gestation, decidual natural killer cells (dNKs) accounts for 70% of the total lymphocytes in this interface, however, the role of its abundance remained unclear.

Recently, Prof. WEI Haiming and Prof. TIAN Zhigang’s team from University of Science and Technology of China of Chinese Academy of Scineces discovered a large number of special natural killer cell subsets which not only lose the killing function, but also promote embryonic development by the secretion of growth factors. The finding, published in Immunity, provides insight into the treatment of limited growth and recurrent miscarriage.

Through genome-wide screening, researchers found that compared with peripheral blood NK cells, early pregnancy dNK cells highly express pleiotrophin (PTN) and osteoglycin (OGN), which are vital growth factors for early embryo development. Moreover, the trigger of their massive growth factor expression lies in the crosstalk with HLA-G from embryonic extra-trophoblast cells.

dNK cells play a part in common clinical pregnancy-related disease such as limited embryonic development and recurrent abortion.

On one hand, the ability to express growth factors of dNK cells is significantly reduced in repeated abortion patients, thus they can no longer support the normal development of early embryos. The deletion of the transcription factor Nfil3 in mouse leads to substantial reduction of NK cells in maternal-fetal interface, indicating important role of Nfil3 in ensuring proper function of CD49a⁺Eomes⁺ NK cell subsets.

On the other hand, the incidence of abortion and embryo growth restriction was even higher in advanced pregnancy. Researchers found that the capacity of secreting growth factors of dNK cells in older mice was significantly decreased, though the population remains quite still.

Facing the challenge, researchers explored an adoptive transfer strategy of specific NK cell subsets for the treatment of embryonic growth restriction and recurrent miscarriage and other related diseases. They induced the decidual-like NK cells with bone marrow hematopoietic stem cells in vitro, then adoptively transfered the cells to mice by intravenous infusion.

Both the aged mice and growth factor deficient mice showed significant improvement in pregnancy outcomes as well as embryo growth, clarifying dNK cells in the decidua as a unique promoter for the physiological function of embryonic development.

The study was funded by the National Natural Science Foundation.