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

Objective: 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). Study design: 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. Results: 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). Conclusion: 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.