Defects in NKG2D ligand expression result in failed tolerance induction at the maternal-fetal interface: a possible cause for recurrent miscarriage.
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.
Department of Laboratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jingzhou 434020, Hubei Province, China. bingmjz@hotmail.com
Bing
B
Mei
Shui-Rong
SR
Zhang
Yong-Ling
YL
Chen
Chang-Fu
CF
Wang
D000026:Abortion, Habitual / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D005260:Female; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D018448:Models, Immunological; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D011247:Pregnancy
D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K