Biology subjects

Pallinger, E.

Publications and source records attributed to Pallinger, E..

2 recordsLinked to original sources

bioRxiv2025

BeWo-derived extracellular vesicles downregulate IL-6Rα expression via miRNAs on CD4+ T lymphocytes

Regulatory T lymphocytes are essential for maternal immunotolerance. Their de novo differentiation in the placenta is regulated by local intercellular interactions involving primed uterine immune cells, fetal syncytiotrophoblasts, and the cytokine environment. Trophoblast-derived, HLA-G-positive extracellular vesicles (EVs) can bind to T lymphocytes, thereby influencing their differentiation and cytokine production. Thus, these EVs play a role in establishing and maintaining a tolerogenic environment. In our study, we used the BeWo choriocarcinoma cell line to model the effects of trophoblast-derived EVs. Large EVs derived from BeWo cells (BeWo-12.5K lEVs) reduce IL-6R expression on CD4+ T cells. This modifies the IL-6 pathway by downregulating the transcription factors STAT3 and NFKB1, and PIAS3, while upregulating STAT1. This may be caused by specific microRNAs (miRNAs), such as hsa-mir-92a-3p, hsa-mir-520f-3p, and hsa-mir-25-3p. These microRNAs are present in BeWo-12.5K lEVs and target the IL-6 pathway. BeWo-12.5K lEVs induce phenotypic and functional changes in T cells, enhancing the ratio of CD4+/CD25+ T cells that produce IL-10. Pregnancy-associated IL-6R downregulation has been demonstrated in clinical samples. Significantly lower levels of IL-6R were detected on circulating CD4+CD25+ T cells in healthy pregnant women than in healthy non-pregnant individuals. This finding reflects the in vivo significance of our in vitro studies. Our studies suggest that communication between maternal and fetal cells significantly influences the development and maintenance of local T cell polarity. The microRNA content of HLA-G+ 12.5K lEVs appears to be key to this process, as it alters the IL-6 pathway.

immunology↗

bioRxiv2022

Initial and ongoing tobacco smoking elicits vascular damage and distinct inflammatory response linked to neurodegeneration

Tobacco smoking is strongly linked to vascular damage contributing to the development of hypertension, atherosclerosis, as well as an increased risk for neurodegeneration. Still, the contribution of the innate immune system to the development of vascular damage upon chronic tobacco use before the onset of clinical symptoms is not fully elucidated. Notably, our data provide evidence that a single acute exposure to tobacco in never smokers elicits a secretion of extracellular vesicles by endothelial cells expressing CD105 and CD49e, granting further recognition of early preclinical biomarker of vascular damage. Further, we investigated the effects of smoking on the immune system of healthy asymptomatic chronic smokers compared to never-smokers and focused on the innate immune system. Our data reveal a distinct immune landscape representative for early stages of vascular damage before tobacco smoking related disease develop in clinically asymptomatic chronic smokers. These results indicate a dysregulated immuno-vascular axis in chronic tobacco smokers that are considered healthy individuals. The distinct alterations are characterized by increased CD36 expression by blood monocyte subsets, neutrophilia, increased plasma IL-18 and reduced levels of IL-33, IL-10 and IL-8. Further, the detection of lower circulating BDNF and elevated sTREM2, specific markers for neurodegeneration, suggests a considerable pre-clinical impact of tobacco smoking on CNS function in clinically healthy individuals. These findings provide further insight into the initial and ongoing effects of tobacco smoking and the potential vascular damage contributing to the progression of neurodegenerative disorders, specifically cerebrovascular dysfunction and dementia.

immunology↗