Different behavior of NK cells isolated from healthy women and women with recurrent spontaneous abortion after treatment with human amniotic epithelial cells

Abstract

Maternal immunotolerance during pregnancy is heavily dependent on the critical properties of human amniotic epithelial cells (hAECs). Recurrent spontaneous abortion (RSA) is one of the most common diseases in women and is caused by feto-maternal immunotolerance disruption. The objective of this study is to investigate how hAEECs affect pNK cells isolated from RSA and healthy women in terms of immunomodulation. Peripheral blood NK cells were isolated from 20 women with RSA and 20 healthy women. Purified NK cells were co-cultured with hAECs, obtained from full-term healthy pregnant women at different cellular ratios. After 24 and 72 h of incubation, the expression of immunomodulatory genes in hAECs, immunophenotype, and cytotoxicity of NK cells, and cytokine production were investigated using real-time PCR, flow cytometry, and ELISA techniques, respectively. We observed a significant increase in TGF-beta and IL-10 production, and CD56bright CD16+ subpopulation in pNK cells, a significant decrease in IFN-gamma production and CD107a and FasL expression on NK cells. Also, NK cells' cytotoxicity against K562 cells was diminished after co-culture with hAECs. The expression of TGF-beta and HLA-G genes by hAECs was diminished after co-culture with NK cells isolated from women with RSA. Our research indicates that the interaction between NK cells and hAECs influences the phenotype and function of both cells. Also, NK cells belonging to women with RSA and healthy women exhibit different behavior during treatment with hAECs, possibly due to NK cell dysfunction. However, extensive research is required to assess NK cell defects and their mutual interaction with hAECs.Crosstalk between hAECs and NK cells is mutual and hAECs diverted the phenotype and function of pNK cells toward dNK cells with low cytotoxicity and increased production of anti-inflammatory cytokines and growth factors. NK cells isolated from women with RSA and healthy women showed different responses to hAECs, probably due to the dysfunction of NK cells in these patients. The immunomodulatory mechanisms of hAECs, including HLA-G expression, are impaired under the impact of NK cells isolated from women with RSA.