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标题：NF-κB regulation in maternal immunity during normal and IUGR pregnancies
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作者：Gaayathri Ariyakumar ; Jonathan M. Morris ; Kelly J. McKelvey 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2021
卷号：11
DOI：10.1038/s41598-021-00430-3
语种：English
出版社：Springer Nature
摘要：Intrauterine Growth Restriction (IUGR) is a leading cause of perinatal death with no effective cure, affecting 5–10% pregnancies globally. Suppressed pro-inflammatory Th1/Th17 immunity is necessary for pregnancy success. However, in IUGR, the inflammatory response is enhanced and there is a limited understanding of the mechanisms that lead to this abnormality. Regulation of maternal T-cells during pregnancy is driven by Nuclear Factor Kappa B p65 (NF-κB p65), and we have previously shown that p65 degradation in maternal T-cells is induced by Fas activation. Placental exosomes expressing Fas ligand (FasL) have an immunomodulatory function during pregnancy. The aim of this study is to investigate the mechanism and source of NF-κB regulation required for successful pregnancy, and whether this is abrogated in IUGR. Using flow cytometry, we demonstrate that p65 + Th1/Th17 cells are reduced during normal pregnancy, but not during IUGR, and this phenotype is enforced when non-pregnant T-cells are cultured with normal maternal plasma. We also show that isolated exosomes from IUGR plasma have decreased FasL expression and are reduced in number compared to exosomes from normal pregnancies. In this study, we highlight a potential role for FasL + exosomes to regulate NF-κB p65 in T-cells during pregnancy, and provide the first evidence that decreased exosome production may contribute to the dysregulation of p65 and inflammation underlying IUGR pathogenesis.