Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells
| Autor: | Xiaoying Jin, Hai-Yi Fei, Anran Yang, Jiajuan Zhu, Songying Zhang, Cuiyu Yang, Jianmin Chen, Huihong Wang, Lingling Jiang, Xiaoyang Fei, Xiu Liu, Chao Li |
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| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
decidual NK Cells HLA-E Angiogenesis Placenta Mice Nude mTORC1 Oxidative phosphorylation Applied Microbiology and Biotechnology Cell Line Tissue Culture Techniques Extracellular Vesicles Interferon-gamma Mice Pregnancy Decidua medicine Animals Humans Secretion Molecular Biology Ecology Evolution Behavior and Systematics Chemistry Histocompatibility Antigens Class I Trophoblast Embryo Cell Biology Extracellular vesicle Trophoblasts Cell biology Killer Cells Natural secretion medicine.anatomical_structure Pregnancy Maintenance embryonic structures Female Research Paper Developmental Biology |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| DOI: | 10.7150/ijbs.63390 |
| Popis: | Extracellular vesicles derived from trophoblasts (T-EVs) play an important role in pregnancy, but the mechanism is not entirely clear. In this study, we found that HLA-E, which is mostly confined to the cytoplasm of trophoblast cells, was secreted by T-EVs. The level of HLA-E in T-EVs from unexplained recurrent spontaneous abortion (URSA) patients was lower than that in normal pregnancy (NP) and RSA patients who had an abnormal embryo karyotype (AK-RSA). T-EVs promoted secretion of IFN-γ and VEGFα by decidual NK (dNK) cells from URSA patients via HLA-E, VEGFα was necessary for angiogenesis and trophoblast growth, and IFN-γ inhibited Th17 induction. Glycolysis and oxidative phosphorylation (OxPhos) were involved in this process. Glycolysis but not OxPhos of dNK cells facilitated by T-EVs was dependent on mTORC1 activation. Inhibition of T-EV production in vivo increased the susceptibility of mice to embryo absorption, which was reversed by transferring exogenous T-EVs. T-EVs promoted secretion of IFN-γ and VEGFα by dNK cells to maintain pregnancy via Qa-1 in abortion-prone mouse models. This study reveals a new mechanism of pregnancy maintenance mediated by HLA-E via T-EVs. |
| Databáze: | OpenAIRE |
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