Human placental exosomes induce maternal systemic immune tolerance in a monocyte-dependent manner
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ABSTRACT:
PROVIDER: PRJNA762864 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15865474.fastq.gz | Fastqsanger.gz | |||
| SRR15865475.fastq.gz | Fastqsanger.gz | |||
| SRR15865476.fastq.gz | Fastqsanger.gz | |||
| SRR15865477.fastq.gz | Fastqsanger.gz | |||
| SRR15865478.fastq.gz | Fastqsanger.gz |
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Project description:Maternal immune tolerance toward to the semi-allograft fetus is a prerequisite condition for successful pregnancy. However, the role of maternal monocytes in the induction of systemic immune tolerance is poorly understood. Here we report that placenta facilitates maternal immune tolerance by extruding exosomes. Maternal monocytes were transformed into an immunosuppressive phenotype after taking up exosomes. Mechanistically, PD-L1 was significantly increased in pEXO-educated monocytes via miRNA-29a-3p/PTEN signaling pathway. In addition, pEXO-treated monocytes could increase Treg pool in maternal blood through a direct cell-cell interaction. Moreover, Th1 cytokines, IFNγ and TNF-α, in monocyte-T cell co-culture system were significantly decreased. Together, our results indicated that maternal monocyte is indispensable components in systemic immune tolerance establishment.
2021-09-16 | GSE184020 | GEO
Project description:BackgroundThe maternal immune system needs to tolerate the semi-allogeneic fetus in pregnancy. The adaptation occurs locally at the maternal-fetal interface as well as systemically through the maternal circulation. Failure to tolerate the paternal antigens may result in pregnancy complications, such as pregnancy loss and pre-eclampsia. However, the mechanism that regulates maternal immune tolerance, especially at the systemic level, is still an enigma. Here we report that the first-trimester placenta-derived exosomes (pEXOs) contribute to maternal immune tolerance by reprogramming the circulating monocytes.ResultspEXOs predominantly target monocytes and pEXO-educated monocytes exhibit an immunosuppressive phenotype as demonstrated by reduced expression of marker genes for monocyte activation, T-cell activation and antigen-process/presentation at the transcriptomic level. They also have a greater propensity towards M2 polarization when compared to the monocytes without pEXO treatment. The inclusion of pEXOs in a monocyte-T-cell coculture model significantly reduces proliferation of the T helper cells and cytotoxic T cells and elevates the expansion of regulatory T cells. By integrating the microRNAome of pEXO and the transcriptomes of pEXO-educated monocytes as well as various immune cell functional assays, we demonstrate that the pEXO-derived microRNA miR-29a-3p promotes the expression of programmed cell death ligand-1, a well-known surface receptor that suppresses the adaptive immune system, by down-regulation of phosphatase and tensin homolog in monocytes.ConclusionsThis is the first report to show how human pEXO directly regulates monocyte functions and its molecular mechanism during early pregnancy. The results uncover the importance of pEXO in regulating the maternal systemic immune response during early pregnancy by reprogramming circulating monocytes. The study provides the basis for understanding the regulation of maternal immune tolerance to the fetal allograft.
| S-EPMC8857816 | biostudies-literature
Project description:Environmental exposure of placental explants did not change the quantity of exosomes or their characteristics. However, exosome cargo composition was changed by specific pollutant to reflect a biochemical signature suggestive of placental nuclear and cellular injury and inflammation.
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Project description:The objective of this study was to investigate whether placental exosomes in gestational diabetes mellitus (GDM) carries a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Exosomes were isolated from chorionic villi-conditioned media and plasma from normal and GDM pregnancies. A specific set of miRNAs was identified to be selectively enriched within exosomes when compared to their cells of origin indicating specific packaging of miRNAs into exosomes. In addition, miRNA expression varies in a consistent pattern in placenta, placental-derived exosomes, circulating exosomes and skeletal muscle in GDM.
2021-03-20 | GSE112168 | GEO
Project description:Placental exosomes polarize human monocyte-derived macrophages to a decidual M2-like macrophage phenotype
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Project description:Prenatal exposure to toxic metals is associated with altered placental function and adverse health outcomes. The underlying mechanisms linking in utero toxic metal exposures with later-in-life health remain unclear, though placental inflammation is posited as a potential driver. The aim of this study was to evaluate whether in utero metals presence is associated with sex-specific changes in placental protein expression. We hypothesized that sex-specific patterns of metal-associated placental protein expression would be observed, and metals presence would be positively associated with the altered expression of inflammation-associated pathways Using samples banked from the Extremely Low Gestational Age Newborn Study (ELGAN), umbilical cord tissue samples were analyzed via ICP-MS/MS for trace elements, and placental samples underwent a global untargeted proteomics analysis via LC-MS/MS. This work highlights the linkage between prenatal metals exposure and an altered placental proteome, revealing that metals in cord tissue were associated with largely distinct differences in placental protein expression, in a sexually-dimorphic manner.
2023-10-24 | PXD041694 | Pride
Project description:Macrophages are abundant in uterine mucosa during the peri-implantation phase and early pregnancy. Decidual macrophages display dynamic changes alone with pregnancy progress: During the peri-implantation phase, macrophages displayed a pro-inflammatory phenotype which facilitates embryo implantation. While, In the late firster trimester and second trimester, decidual macrophages are anti-proinflammatory which are helpful to pregnancy maintenance. Alterations in the ratio of pro-inflammatory/anti-inflammatory decidual macrophages lead to abortion, preeclampsia, and preterm birth. Placenta-derived exosomes (pEXO) are critical in the immune cell modulation such as T cell apoptosis, NK activities, and T regulatory (Treg) differentiation. However, it is unknown whether placenta-derived exosomes contribute to decidual macrophage polarization during early pregnancy. Here we report that exosomes from the placenta explant stimulate M2 macrophage polarization via exosomal miRNA-30d-5p. Mechanistically, miRNA-30d-5p polarized macrophages to M2 phenotype by inhibiting HDAC9 expression. Furthermore, the conditioned medium of pEXO-treated macrophages promoted trophoblast migration and invasion. By contrast, conditioned medium impaired the ability of endothelial cell tube formation. However, pEXO-treated macrophages have no impact on T cell proliferation. Together, we demonstrated that pEXO promoted trophoblast migration and invasion, endothelial cell migration, and attenuation of endothelial cell tube formation by polarizing macrophage to decidua-like macrophage.
2021-09-16 | GSE184194 | GEO
Project description:The goal of this study is to report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC Loading Complex (RLC) and display cell-independent capacity to process precursor microRNAs (pre-miRNAs) into mature miRNAs. Pre-miRNAs, along with Dicer, AGO2, and TRBP, are present in exosomes of cancer cells. CD43 mediates the accumulation of Dicer specifically in cancer exosomes. Cancer exosomes mediate an efficient and rapid silencing of mRNAs to reprogram the target cell transcriptome. Exosomes derived from cells and sera of patients with breast cancer instigate non-tumorigenic epithelial cells to form tumors in a Dicer-dependent manner. These findings offer opportunities for the development of exosomes based biomarkers and therapies. Exosomes from cancer cells and non-tumorigenic cells were isolated using established ultracentrifugation methods. The global miRNA content of cancer exosomes and normosomes was investigated. Profiling of cells themselves was also used as a control. Exosomes with Dicer down regulation (MCF10AshDicer and MDA-MB-231shDicer exosomes), as well as MDA-MB-231 exosomes that contain a Dicer antibody inside were used to study the function Dicer protein in the microRNA biogenesis in exosomes.
2014-08-27 | E-GEOD-60714 | biostudies-arrayexpress
Project description:During pregnancy, the placenta forms the interface between mother and fetus. Highly controlled regulation of trans-placental trafficking is therefore essential for the healthy development of the growing fetus. Extracellular vesicle-mediated transfer of protein and nucleic acids from the human placenta into the maternal circulation is well documented; the possibility that this trafficking is bi-directional has not yet been explored but could affect placental function and impact on the fetus.We hypothesized that the ability of the placenta to respond to maternal inflammatory signals is mediated by the interaction of maternal immune cell exosomes with placental trophoblast. Utilizing the BeWo cell line and whole placental explants, we demonstrated that the human placenta internalizes macrophage-derived exosomes in a time- and dose-dependent manner. This uptake was via clathrin-dependent endocytosis. Furthermore, macrophage exosomes induced release of proinflammatory cytokines by the placenta. Taken together, our data demonstrates that exosomes are actively transported into the human placenta and that exosomes from activated immune cells modulate placental cytokine production. This represents a novel mechanism by which immune cells can signal to the placental unit, potentially facilitating responses to maternal inflammation and infection, and thereby preventing harm to the fetus.
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