Elsa Bernier, Camille Couture, Anna Borchers, Marie-Eve Brien, Charles H Graham, Sylvie Girard
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We performed cocultures between circulating immune cells and HUVECs to assess endothelial activation. We found that EOPE had decreased regulatory T cells (4.64±0.33, p < 0.05) and monocytes (33.92±3.08, p < 0.01), whereas LOPE had decreased regulatory T cells (4.60±0.30, p < 0.05) and Th2 cells (7.50±0.62, p < 0.01) versus CTRL. Compared to CTRL, elevated cytokines/chemokines, and growth factors were observed in LOPE, whereas EOPE primarily showed decreased levels. Using intracellular cytokine staining, we observed more monocytes producing IL-12, TNF-α, and IL-1β (all p < 0.05) in LOPE versus CTRL. At the transcriptomic level, we found differentially expressed genes between EOPE and CTRL, predominantly related to upregulation of immune activation pathways. Lastly, EOPE PBMCs induced heightened endothelial activation in vitro observed by increased ICAM-1 and ET-1 (p < 0.05), whereas LOPE PBMCs required LPS stimulation. Although significant proteomic changes are observed in the LOPE group, the EOPE displayed changes mostly at the transcriptomic levels and could induce endothelial activation in vitro.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Circulating Immune Cells from Early- and Late-onset Pre-eclampsia Displays Distinct Profiles with Differential Impact on Endothelial Activation.\",\"authors\":\"Elsa Bernier, Camille Couture, Anna Borchers, Marie-Eve Brien, Charles H Graham, Sylvie Girard\",\"doi\":\"10.4049/jimmunol.2400196\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Pre-eclampsia (PE) affects 5-8% of pregnancies and has detrimental effects on maternal-fetal health. PE is characterized by de novo hypertension after 20 wk of gestation and end-organ damage. Systemic inflammatory imbalance has been associated with PE, but its contribution to the pathology is poorly understood. Our objective was to investigate maternal systemic immune changes in early-onset PE (EOPE) and late-onset PE (LOPE) versus uncomplicated pregnancies (control [CTRL]), and their contribution to endothelial activation, hallmark of hypertension. Blood samples were analyzed by flow cytometry, multiplex assay, intracellular cytokine staining, and single-cell RNA sequencing. We performed cocultures between circulating immune cells and HUVECs to assess endothelial activation. We found that EOPE had decreased regulatory T cells (4.64±0.33, p < 0.05) and monocytes (33.92±3.08, p < 0.01), whereas LOPE had decreased regulatory T cells (4.60±0.30, p < 0.05) and Th2 cells (7.50±0.62, p < 0.01) versus CTRL. Compared to CTRL, elevated cytokines/chemokines, and growth factors were observed in LOPE, whereas EOPE primarily showed decreased levels. Using intracellular cytokine staining, we observed more monocytes producing IL-12, TNF-α, and IL-1β (all p < 0.05) in LOPE versus CTRL. At the transcriptomic level, we found differentially expressed genes between EOPE and CTRL, predominantly related to upregulation of immune activation pathways. Lastly, EOPE PBMCs induced heightened endothelial activation in vitro observed by increased ICAM-1 and ET-1 (p < 0.05), whereas LOPE PBMCs required LPS stimulation. 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引用次数: 0
摘要
子痫前期(PE)影响到 5%-8%的孕妇,对母婴健康造成不利影响。子痫前期的特征是妊娠 20 周后出现新发高血压和内脏器官损伤。全身炎症失衡与 PE 有关,但其对病理的影响还不甚了解。我们的目的是研究早发型 PE(EOPE)和晚发型 PE(LOPE)与无并发症妊娠(对照组 [CTRL])的母体全身免疫变化,以及它们对高血压标志物--内皮活化的贡献。血液样本通过流式细胞术、多重检测、细胞内细胞因子染色和单细胞 RNA 测序进行分析。我们将循环免疫细胞与 HUVECs 进行共培养,以评估内皮活化情况。我们发现,EOPE 减少了调节性 T 细胞(4.64±0.33,p
Circulating Immune Cells from Early- and Late-onset Pre-eclampsia Displays Distinct Profiles with Differential Impact on Endothelial Activation.
Pre-eclampsia (PE) affects 5-8% of pregnancies and has detrimental effects on maternal-fetal health. PE is characterized by de novo hypertension after 20 wk of gestation and end-organ damage. Systemic inflammatory imbalance has been associated with PE, but its contribution to the pathology is poorly understood. Our objective was to investigate maternal systemic immune changes in early-onset PE (EOPE) and late-onset PE (LOPE) versus uncomplicated pregnancies (control [CTRL]), and their contribution to endothelial activation, hallmark of hypertension. Blood samples were analyzed by flow cytometry, multiplex assay, intracellular cytokine staining, and single-cell RNA sequencing. We performed cocultures between circulating immune cells and HUVECs to assess endothelial activation. We found that EOPE had decreased regulatory T cells (4.64±0.33, p < 0.05) and monocytes (33.92±3.08, p < 0.01), whereas LOPE had decreased regulatory T cells (4.60±0.30, p < 0.05) and Th2 cells (7.50±0.62, p < 0.01) versus CTRL. Compared to CTRL, elevated cytokines/chemokines, and growth factors were observed in LOPE, whereas EOPE primarily showed decreased levels. Using intracellular cytokine staining, we observed more monocytes producing IL-12, TNF-α, and IL-1β (all p < 0.05) in LOPE versus CTRL. At the transcriptomic level, we found differentially expressed genes between EOPE and CTRL, predominantly related to upregulation of immune activation pathways. Lastly, EOPE PBMCs induced heightened endothelial activation in vitro observed by increased ICAM-1 and ET-1 (p < 0.05), whereas LOPE PBMCs required LPS stimulation. Although significant proteomic changes are observed in the LOPE group, the EOPE displayed changes mostly at the transcriptomic levels and could induce endothelial activation in vitro.
期刊介绍:
The JI publishes novel, peer-reviewed findings in all areas of experimental immunology, including innate and adaptive immunity, inflammation, host defense, clinical immunology, autoimmunity and more. Special sections include Cutting Edge articles, Brief Reviews and Pillars of Immunology. The JI is published by The American Association of Immunologists (AAI)