Natural killer (NK) cells are a subset of lymphocytes that contribute to the innate immunity through secretion of cytokines and cell killing cytolytic enzymes. In human, two populations of peripheral NK cells can be distinguished: the cytotoxic NK cells expressing CD56^dimCD16⁺, and the cytokine producing NK cells, expressing CD56^brightCD16^–. During pregnancy, decidual NK (dNK) cells are the most prominent immune cells present in the placental bed¹. dNK cells resemble the cytokine producing NK cells in terms of their CD56 and CD16 cell surface expression, but in contrast to peripheral NK cells they are weakly cytotoxic and express different markers².

During pregnancy, dNK cells exist primarily during the first trimester and gradually decline after the placenta is formed. By the third trimester, T cells become the predominate lymphocyte population at the maternal-fetal interface¹. Interaction of dNK cell-specific receptors with their ligands expressed on either invasive stromal cells or trophoblasts modulate unique functional effects of dNK cells including promotion of placental vascular growth, decidualization, trophoblast invasion and maintaining the immune balance at the maternal-fetal interface³.

Effector functions of dNK cells are regulated by expression of inhibitory and activating receptors which interact with trophoblast HLA Class I molecules (HLA-C/G/E)⁴. Inhibitory and activating receptors expressed on the dNK cells are killer-cell immunoglobulin-like receptors (KIR) and natural killer group (NKG) receptors 2 A/ C/ E and D². Binding of KIR receptors to trophoblast HLA molecules is important for trophoblast migration and spiral artery remodeling⁵. It seems that a lack of KIR expression on dNK cells might be associated with impaired trophoblast invasion, spiral artery remodeling and increasing risk of developing pre-eclampsia⁶.

Besides various receptor-ligand interactions, dNK cells produce many factors such as cytokines (TNF-α, IL-10, and IFN-γ), growth factors (macrophage-colony stimulating factor (M-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and placental growth factor (PlGF)), and angiogenic factors (vascular endothelial growth factor-C (VEGF-C), and angiopoietin-2)^7-9. These factors play an important role in spiral artery remodeling.

The most important phenotypic markers, and cytokines to identify peripheral and decidual NK cells are listed below. Are you interested in other markers, different fluorochromes or need help creating a panel for your research purpose? Contact us at techsupport@iqproducts.nl.

References

• Williams, P. J., et al. 2009. Decidual leucocyte populations in early to late gestation normal human pregnancy. J. Reprod. Immunol. 82: 24–31.

• Koopman, L.A., et al. Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential, J. Exp. Med. 198 (8) (2003) 1201–1212.

• Hanna J., et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface, Nat Med, 2006, vol. 12  (pg. 1065-1074)

• King, S.E., et al. Recognition of trophoblast HLA class I molecules by decidual NK cell receptorsea review, Placenta 21 (Suppl A) (2000) S81eS85.

• Xiong, S., et al. Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation, J. Clin. Invest. 123 (10) (2013) 4264–4272.

• Hiby, S.E., et al. Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success, J. Exp. Med. 200 (8) (2004) 957–965.

• Lash, G.E., et al. Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy, J. Leukoc. Biol. 80 (3) (2006) 572–580.

• Jokhi, P.P., et al. Production of granulocyte-macrophage colonystimulating factor by human trophoblast cells and by decidual large granular lymphocytes, Hum. Reprod. 9 (9) (1994) 1660–1669.

• Saito, S., et al. Cytokine production by CD16-CD56bright natural killer cells in the human early pregnancy decidua, Int. Immunol. 5 (5) (1993) 559–563.