Wallace Alison E, Whitley Guy S, Thilaganathan Baskaran, Cartwright Judith E
Institute of Cardiovascular and Cell Sciences, St George's University of London, United Kingdom; and.
Fetal Medicine Unit, St George's Hospital, London, United Kingdom.
J Leukoc Biol. 2015 Jan;97(1):79-86. doi: 10.1189/jlb.2A0614-282R. Epub 2014 Nov 7.
During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor blocking in trophoblast coculture and altered dNK expression of the cytokines CXCL10 and TNF-α, which regulate trophoblast behavior. These results indicate that dNK cells from high RI pregnancies may display altered interactions with trophoblast via decreased expression of HLA-binding cell-surface receptors, impacting on successful transformation of the uterus for pregnancy.
在怀孕期间,一种特殊类型的自然杀伤(NK)细胞在子宫内膜(蜕膜)中聚集,并与半同种异体的胎儿滋养层细胞相互作用。蜕膜自然杀伤(dNK)细胞在功能和表型上与外周血NK细胞不同,并且参与子宫螺旋动脉滋养层转化的调节,若该调节不充分,可能导致妊娠疾病。在此,我们在妊娠早期使用子宫动脉多普勒阻力指数(RI)作为螺旋动脉转化程度的替代指标,以识别RI值高的妊娠,这表明螺旋动脉重塑受损。我们使用流式细胞术检测从这些妊娠中分离出的dNK细胞,并与RI正常的妊娠中的dNK细胞进行比较。我们报告称,RI值高的妊娠中,表达KIR2DL/S1、3、5和LILRB1(滋养层上HLA - C和HLA - G的受体)的dNK细胞比例降低。通过在滋养层共培养中进行受体阻断,检测蜕膜中LILRB1表达的降低情况,以及调节滋养层行为的细胞因子CXCL10和TNF - α的dNK表达变化。这些结果表明,RI值高的妊娠中的dNK细胞可能通过降低HLA结合细胞表面受体的表达,表现出与滋养层的相互作用改变,从而影响子宫为妊娠成功进行的转化。