Defects in NKG2D ligand expression result in failed tolerance induction at the maternal-fetal interface: a possible cause for recurrent miscarriage

Abstract

Certain maternal immune responses against the fetus at the maternal-fetal interface may contribute to recurrent miscarriage (RM). Trophoblast cells involve in forming of maternal-fetal interface and interact with many immune cells, including NK cells. NK cells accumulate at the maternal-fetal interface and play a critical role during pregnancy. NKG2D ligands can activate NK cells through engaging with corresponding receptors. The 5'-end flanking regions of DNA sequence of some NKG2D ligands contain heat shock elements. It is very possible that oxidative stress, produced in pathological process of RM, induces abnormal NKG2D ligand expression in the trophoblast cells, which stimulate cytotoxicity of NK cells. Moreover, in normal pregnancy, soluble NKG2D ligands are secreted into sera by syncytiotrophoblast cells, which disturb NKG2D-mediated maternal anti-fetus immunity. Reduction of soluble NKG2D ligand levels in association with upregulation of NKG2D on immune cells may also contribute to pathogenesis of RM.