PhD Scientific Days 2026

Poster Session 3.W - Pharmaceutical Sciences and Health Technologies

Trophoblast-derived Extracellular Vesicles in the Regulation of Maternal Immunotolerance

Name of the presenter

Németh, Júlia

Institute/workplace of the presenter

Institute of Genetics, Cell-, and Immunobiology, Semmelweis University

Authors

Júlia Németh¹, Nóra Fekete¹, Bence Nagy¹, Éva Pállinger¹
1: Institute of Genetics, Cell-, and Immunobiology, Semmelweis University

Text of the abstract

Maternal immunotolerance of the ‘semi-allogeneic’ fetus, is maintained through tightly regulated crosstalk between trophoblasts and maternal immune cells. This bidirectional communication is frequently mediated by extracellular vesicles (EVs), nanoscale, membrane-bound particles released from cells, that lack the capacity of self-replication.
By interacting with immune cells, EVs can modulate the immune response, making them key mediators of immunosuppression.
The close interdependence between immune function and metabolism highlights the significance of assessing the activation status and metabolic activity of immune cells, yielding critical insights into their function and interactions with the maternal milieu.

We aimed to investigate the glucose metabolic changes in T cells induced by trophoblast (BeWo choriocarcinoma cell-line)-derived EVs to contribute to the understanding of trophoblast-lymphocyte interaction in the development of maternal immunotolerance.

Medium-sized (~300 nm) EVs were isolated from BeWo cells using differential centrifugation. Lymphocytes obtained from childless women under the age of 40 were separated by density gradient centrifugation, activated via CD3/CD28-stimulation (DynabeadsTM), and treated with BeWo EVs.
Immunophenotyping with fluorescence-conjugated antibodies enabled the characterization of lymphocyte subpopulations based on the cell-specific markers. Flow cytometry was employed to assess the effect of BeWo EVs on the activation (activation marker CD25 signal) and glucose uptake (2-NBDG glucose-analogue signal) of CD4+ and CD8+ T cell subsets.
In addition, the impact of BeWo EVs on glucose metabolism at the transcriptome level was evaluated using a qPCR array.

We observed the tendencies that BeWo EVs reduced CD25 expression and decreased 2-NBDG uptake in both Th and Tc cells. Furthermore, the majority of analyzed genes were involved in glycolysis and showed a downregulated expression upon exposure to BeWo EV.

These findings suggest that EVs of a trophoblast cell-line (BeWo) suppress maternal CD4+ T cell activation, by reducing CD25 expression and glucose metabolic activity. These imply that trophoblast EVs may modulate immune cell function toward a more tolerogenic function (and phenotype), thereby contributing to the establishment of maternal immunotolerance.

This research did not receive any targeted funding.