Abnormal expression of ILT2, NKG2D and NKp46 receptors on natural killer cells in women with unexplained recurrent implantation failure.

Recurrent implantation failure (RIF) refers to the repeated failures of embryo implantation during assisted reproductive technology and half of them remain unexplained (uRIF). Evidence has proven the association between uRIF and immune dysregulation related with natural killer (NK) cells. The aim of this study was to explore the expression of cytotoxic granules, activation and inhibitory receptors within NK cell subsets in both peripheral blood (pbNK) and uterine (uNK) samples during the embryo implantation phase of the menstrual cycle in women with uRIF and live birth (LB). 25 pregnant women who achieved live birth (LB group) and 13 patients with uRIF (uRIF group) were recruited. The expression of ILT2, NKp46, NKp44, NKp30, NKG2D, KIR2DL2/S2/L3, as well as intracellular cytotoxicity granules (perforin and granzyme B) on pbNK and uNK subsets were assessed by flow cytometry. Compared to LB group, the expression of ILT2 receptor on CD56dimCD16bright uNK, NKG2D receptors on CD56dimCD16dim and CD56dimCD16bright uNK were significantly lower in uRIF patients, while the expression of NKp46 receptor on both CD56dimCD16+ pbNK and CD56dimCD16bright uNK subsets were significantly higher in uRIF patients. However, there were no significant difference of perforin and Granzyme B expression in pbNK or uNK cells or their subsets between uRIF and LB groups. The altered expression of ILT2, NKG2D and NKp46 receptors on pbNK and uNK cell subsets might imply the associations between the abnormally expressed activation and inhibitory receptors in NK cell subsets and embryo implantation failure.