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Upregulated TRAIL and Reduced DcR2 Mediate Apoptosis of Decidual PMN-MDSC in Unexplained Recurrent Pregnancy Loss.
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2020-05-27 , DOI: 10.3389/fimmu.2020.01345
Congcong Li 1, 2 , Xiaoxin Zhang 1 , Xiaomin Kang 3 , Chao Chen 1, 2 , Feng Guo 1, 2 , Qiaohong Wang 1, 2 , Aimin Zhao 1, 2
Affiliation  

Myeloid-derived suppressor cells (MDSC), especially polymorphonuclear MDSC (PMN-MDSC), accumulate in maternal-fetal interface during pregnancy and are involved in the maintenance of immune tolerance. Decreased PMN-MDSC is associated with pregnancy complications such as unexplained recurrent pregnancy loss (URPL). In the present study we showed decreased PMN-MDSC in the URPL group compared with the normal pregnancy (NP) group, and PMN-MDSC was the major subset of MDSC in human decidua with potent immune suppression activity. We then performed gene expression profile and found that human decidual PMN-MDSC in the NP and URPL groups showed different gene and pathway signature, including apoptosis. Apoptosis of decidual PMN-MDSC was mediated by TNF-related apoptosis–induced ligand (TRAIL) in a Caspase 3 dependent manner. TRAIL was expressed in decidua and upregulated in decidua of the URPL group. Notably, of all the membrane TRAIL receptors, only DcR2 was down-regulated in PMN-MDSC in the URPL group. In vitro experiment demonstrated that DcR2 blockade sensitized PMN-MDSC to TRAIL-mediated apoptosis. Together, these data indicate that increased TRAIL and reduced DcR2 on PMN-MDSC sensitize PMN-MDSC response to TRAIL-induced apoptosis in the URPL group, which is responsible for decreased accumulation of PMN-MDSC in URPL.



中文翻译:

TRAIL上调和DcR2减少介导无法解释的复发性妊娠丢失中蜕膜PMN-MDSC的凋亡。

骨髓来源的抑制细胞(MDSC),尤其是多形核MDSC(PMN-MDSC),在妊娠期间在母胎界面中积聚,并参与维持免疫耐受性。PMN-MDSC降低与妊娠并发症,例如无法解释的反复妊娠丢失(URPL)有关。在本研究中,我们显示与正常妊娠(NP)组相比,URPL组的PMN-MDSC降低,并且PMN-MDSC是人蜕膜中MDSC的主要子集,具有强大的免疫抑制活性。然后,我们进行了基因表达谱分析,发现NP和URPL组的人蜕膜PMN-MDSC显示出不同的基因和途径特征,包括凋亡。蜕膜性PMN-MDSC的凋亡是由Caspase 3依赖性的TNF相关的凋亡诱导配体(TRAIL)介导的。TRAIL在URPL组的蜕膜中表达,并在其蜕膜中上调。值得注意的是,在所有膜TRAIL受体中,URPL组的PMN-MDSC中只有DcR2被下调。体外实验证明,DcR2阻断使PMN-MDSC对TRAIL介导的细胞凋亡敏感。总之,这些数据表明,在URPL组中,PMN-MDSC上TRAIL的增加和DcR2的减少使PMN-MDSC对TRAIL诱导的细胞凋亡的反应敏感,这是造成URPL中PMN-MDSC积累减少的原因。

更新日期:2020-06-30
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