{
  "abstract": "Problem\n\nA 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\n\nCirculating 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\n\nBeWo-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\n\nOur 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.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.",
    "Heart and Vascular Center, Semmelweis University, Budapest, Hungary.",
    "Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.",
    "MTA-SE Immune-Proteogenomics Extracellular Vesicle Research Group, Budapest, Hungary.",
    "HCEMM-SE Extracellular Vesicle Research Group, Budapest, Hungary."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gábor Seregélyes",
      "orcid": "0009-0007-6558-638X"
    },
    {
      "affs": [
        0
      ],
      "name": "Bence Nagy"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Árpád Ferenc Kovács",
      "orcid": "0000-0002-7742-160X"
    },
    {
      "affs": [
        0
      ],
      "name": "Nóra Fekete",
      "orcid": "0000-0001-9721-765X"
    },
    {
      "affs": [
        0,
        3,
        4
      ],
      "name": "Edit I Buzás",
      "orcid": "0000-0002-3744-206X"
    },
    {
      "affs": [
        0
      ],
      "name": "Éva Pállinger",
      "orcid": "0000-0002-5789-0951"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bqvjxxvxs9k6x.bib",
  "cited_by": 0,
  "doi": "10.1111/aji.70335",
  "fulltext_url": "https://europepmc.org/articles/PMC13677083",
  "id": "bqvjxxvxs9k6x",
  "issns": [
    "1046-7408",
    "1600-0897"
  ],
  "landing_url": "https://europepmc.org/article/MED/42893527",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7222905656",
  "pdf_url": "https://europepmc.org/articles/PMC13677083?pdf=render",
  "pmcid": "PMC13677083",
  "pmid": "42893527",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bqvjxxvxs9k6x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42893527",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42893527"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Extracellular vesicles in disease",
      "subfield": "molecular-biology"
    }
  ],
  "title": "BeWo-Derived Extracellular Vesicles Downregulate IL-6Rα Expression via miRNAs on CD4+ T Lymphocytes.",
  "title_text": "BeWo-Derived Extracellular Vesicles Downregulate IL-6Rα Expression via miRNAs on CD4+ T Lymphocytes.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/bqvjxxvxs9k6x",
  "venue": "American journal of reproductive immunology (New York, N.Y. : 1989)",
  "versions": []
}