BeWo-Derived Extracellular Vesicles Downregulate IL-6Rα Expression via miRNAs on CD4+ T Lymphocytes.
5 affiliations
- 1Institute of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
- 2Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
- 3Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
- 4MTA-SE Immune-Proteogenomics Extracellular Vesicle Research Group, Budapest, Hungary.
- 5HCEMM-SE Extracellular Vesicle Research Group, Budapest, Hungary.
Abstract
Problem
A balanced Th1/Th2/Th17/Treg status is necessary for a successful pregnancy. T cell polarization depends on the local cytokine environment and the responsiveness of T lymphocytes to cytokines. Trophoblast-derived extracellular vesicles (EVs) influence the function of maternal T lymphocytes, contributing to their polarization into the Treg phenotype. We examined whether BeWo-derived EVs affect T cell IL-6 responsiveness using the BeWo cell line as an experimental model and characterized the molecular cargo of BeWo -EVs that may contribute to this process.Methods
Circulating lymphocytes from non-pregnant women were treated with BeWo-EVs or co-cultured with BeWo cells. We detected IL-6Rα expression by flow cytometry and IL6R signaling pathways by RT-PCR. The microRNA (miRNA) content of BeWo EVs was identified by sequencing. Finally, we compared IL-6Rα expression levels in circulating T lymphocytes from healthy pregnant and non-pregnant women.Results
BeWo-EVs reduced IL-6Rα expression on CD4+ T cells. This modifies the IL-6 pathway by downregulating the transcription factors STAT3, NFKB1, and PIAS3 while upregulating STAT1. This may be due to the presence of specific microRNAs (miRNAs), such as hsa-mir-92a-3p, hsa-mir-520f-3p, and hsa-mir-25-3p, in BeWo-EVs that target the IL-6 pathway. Treatment with BeWo-EVs also induced phenotypic and functional changes in T cells and enhanced the ratio of CD4+/CD25+ T cells that produce IL-10. Pregnancy-associated IL-6Rα downregulation has been demonstrated in clinical samples. Significantly lower levels of IL-6Rα were detected on circulating CD4+CD25+ T cells in healthy pregnant women compared to healthy non-pregnant individuals.Conclusions
Our studies suggest that the microRNA content of trophoblast-derived EVs significantly influences the local polarization of maternal T lymphocytes by modifying the IL-6Rα signaling pathway.
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BibTeX
@article{seregelyes2026bewoderived,
title = {{BeWo-Derived Extracellular Vesicles Downregulate IL-6Rα Expression via miRNAs on CD4+ T Lymphocytes.}},
author = {Gábor Seregélyes and Bence Nagy and Árpád Ferenc Kovács and Nóra Fekete and Edit I Buzás and Éva Pállinger},
journal = {American journal of reproductive immunology (New York, N.Y. : 1989)},
year = {2026},
month = oct,
doi = {10.1111/aji.70335},
url = {https://europepmc.org/article/MED/42893527},
note = {CC BY},
}
RIS
TY - JOUR
TI - BeWo-Derived Extracellular Vesicles Downregulate IL-6Rα Expression via miRNAs on CD4+ T Lymphocytes.
AU - Gábor Seregélyes
AU - Bence Nagy
AU - Árpád Ferenc Kovács
AU - Nóra Fekete
AU - Edit I Buzás
AU - Éva Pállinger
PY - 2026
DA - 2026/10/01
JO - American journal of reproductive immunology (New York, N.Y. : 1989)
DO - 10.1111/aji.70335
UR - https://europepmc.org/article/MED/42893527
AB - Problem A balanced Th1/Th2/Th17/Treg status is necessary for a successful pregnancy. T cell polarization depends on the local cytokine environment and the responsiveness of T lymphocytes to cytokines. Trophoblast-derived extracellular vesicles (EVs) influence the function of maternal T lymphocytes, contributing to their polarization into the Treg phenotype. We examined whether BeWo-derived EVs affect T cell IL-6 responsiveness using the BeWo cell line as an experimental model and characterized the molecular cargo of BeWo -EVs that may contribute to this process.Methods Circulating lymphocytes from non-pregnant women were treated with BeWo-EVs or co-cultured with BeWo cells. We detected IL-6Rα expression by flow cytometry and IL6R signaling pathways by RT-PCR. The microRNA (miRNA) content of BeWo EVs was identified by sequencing. Finally, we compared IL-6Rα expression levels in circulating T lymphocytes from healthy pregnant and non-pregnant women.Results BeWo-EVs reduced IL-6Rα expression on CD4+ T cells. This modifies the IL-6 pathway by downregulating the transcription factors STAT3, NFKB1, and PIAS3 while upregulating STAT1. This may be due to the presence of specific microRNAs (miRNAs), such as hsa-mir-92a-3p, hsa-mir-520f-3p, and hsa-mir-25-3p, in BeWo-EVs that target the IL-6 pathway. Treatment with BeWo-EVs also induced phenotypic and functional changes in T cells and enhanced the ratio of CD4+/CD25+ T cells that produce IL-10. Pregnancy-associated IL-6Rα downregulation has been demonstrated in clinical samples. Significantly lower levels of IL-6Rα were detected on circulating CD4+CD25+ T cells in healthy pregnant women compared to healthy non-pregnant individuals.Conclusions Our studies suggest that the microRNA content of trophoblast-derived EVs significantly influences the local polarization of maternal T lymphocytes by modifying the IL-6Rα signaling pathway.
SN - 1046-7408
SN - 1600-0897
ER -