Differences in the Expression of KIR, ILT Inhibitory Receptors, and VEGF Production in the Induced Decidual NK Cell Cultures of Fertile and RPL Women

Abstract

Results: KIR2DL1 and ILT-2 expression on idNK cells was higher in healthy women than in RPL patients. Sildenafil enhanced NKG2A expression in RPL patients. VEGF concentration was higher in fertile woman idNK cell cultures. idNK cells were more sensitive for necrosis in RPL than in fertile women. SC did not influence VEGF production or idNK cell apoptosis.

Conclusions: A combination of hypoxia, IL-15, and AZA promotes the conversion of pbNK into idNK cells CD56⁺CD16^--expressing KIR receptors and produces VEGF. Alterations in KIR2DL1 and ILT-2 expression as well as impaired VEGF production were associated with RPL. SC affects NKG2A expression on RPL idNK cells. SC had no effect on VEGF release or idNK cell apoptosis.

Figure 1

The expression of KIR receptors KIR2DL1, NKG2A, and ILT-2 and the coexpression of NKG2A with KIR2DL1 on idNK cells cultured with 400 ng/ml of sildenafil citrate (SC). CG: control group: (a) n = 22, (b) n = 24, (c) n = 23, and (d) n = 17; RPL: recurrent pregnancy loss patients: (a) n = 20, (b) n = 22, (c) n = 18, and (d) n = 14.

Figure 2

The stages of apoptosis of idNK cells after 7 days of culturing with and without 400 ng/ml of sildenafil citrate (SC). The results are presented as the mean + SD of the percentage of cells at different stages of apoptosis: green boxes, CG idNK cells in transformation media; deep green, CG idNK cells in transformation media supplemented with SC; blue boxes, RPL idNK cells in transformation media; and deep blue boxes, RPL idNK cells media supplemented with SC (CG: control group, n = 14; RPL: recurrent pregnancy loss women, n = 12).

Figure 3

The level of VEGF in the culture supernatants of idNK cells (CG: control group, RPL: recurrent pregnancy loss women, and SC: sildenafil citrate; data shown as mean and SD).