Increased expression of Toll-like receptor 3 in decidual natural killer cells of patients with unexplained recurrent spontaneous miscarriage

Abstract

To investigate whether the expression of Toll-like receptor 3 (TLR3) in decidual natural killer (dNK) cells plays a role in the pathogenesis of unexplained recurrent spontaneous miscarriage (URSM). NK cells were isolated from human decidual tissue through magnetic cell sorting and analyzed for phenotypes through flow cytometry. TLR3 expression in dNK cells was detected by quantitative reverse-transcriptase polymerase chain reaction and western blotting. The cytotoxicity of dNK was detected using a lactate dehydrogenase release test. The CD56(+) dNK percentages varied between 85% and 96%. The expression of TLR3 mRNA and protein in dNK cells of URSM patients was statistically significantly higher than that in control women (p=0.005 and p=0.01, respectively). Meanwhile, the mean cytotoxicity percentage of freshly isolated dNK cells from the patients was significantly higher than that from normal controls (31.24 ± 7.46% vs. 16.20 ± 6.03%; p=0.03). The expression of TLR3 in dNK cells is abnormally higher in URSM patients, which indicates that TLR3 expression may be critical to the activation of dNK cells infiltrating the maternal-fetal interface and account for the loss of immune tolerance.