Author Of 1 Presentation
P1115 - A first characterization of placenta-derived extracellular vesicles in patients with multiple sclerosis. (ID 1909)
Abstract
Background
Pregnancy is a condition of complex immunomodulation during which multiple sclerosis (MS) significantly improves. The molecular mechanisms behind this phenomenon have not been completely elucidated. A central role is played by the placenta and its released factors such as the extracellular vesicles (EV), a peculiar mechanism of communication and material exchange between cells. Studies conducted on an experimental murine model of MS have shown that EV shed into the blood during pregnancy have an inhibitory effect on the proliferation of T cells.
Objectives
To characterize the surface markers expressed by the EV secreted by the maternal (decidua) and fetal (trophoblast) side of the placenta of patients with MS and healthy donors (HC), and to evaluate the effects of the EV on the activation status of CD14+ monocytes and the activity of regulatory T lymphocytes (Treg).
Methods
Total EV shed by placental samples from 15 women with MS and 14 HC were isolated by ultracentrifugation, quantified by Nanoparticle Tracking Analysis and characterized by flow cytometry for the expression of 37 surface markers using the human MACSPlex Exosome Kit. CD14+ monocytes, Treg end CD4+ T cells were isolated from HC buffy coats. CD14+ monocytes were activated with LPS and the expression levels of pro and anti-inflammatory cytokines was evaluated by real-time PCR. CD4+ T cells were activated via CD3 and CD28 and their proliferation activity was evaluated by BrdU Cell Proliferation Assay after co-culture with EV-conditioned Treg.
Results
Most of the analyzed surface markers resulted differentially expressed between the EV released by decidua or trophoblast, but not between the EV shed by placental tissues of MS patients or HC, except for CD133, whose level was higher in the EV secreted by trophoblast of women with MS. The conditioning with EV shed by placenta samples of MS patients was able to moderately decrease the expression level of pro-inflammatory cytokines by activated CD14+ monocytes and the proliferation activity of CD4+ T cells, although the effect was not statistically significant.
Conclusions
For the first time to our knowledge, this study enabled a preliminary characterization of the EV shed by placental tissues of patients with MS. However, further studies are needed to clarify the role of placental EV in the pregnancy-related improvement of the MS disease.