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High levels of circulating extracellular vesicles with altered expression and function during pregnancy
Fabiola da Silva Nardi1, Tatiana Ferreira Michelon2, Jorge Neumann2
1Genetics Department, Laboratory of Immunogenetics and Histocompatibility (LIGH), Federal University of Paraná, 19031 Curitiba, Brazil; Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany; CAPES Foundation, Ministry of Education of Brazil, Brasília-DF 70, 040-020, Brazil.
Immunobiology
|March 24, 2016
Summary
Circulating extracellular vesicles (EVs) increase during pregnancy and carry higher levels of immunosuppressive cytokines. These pregnancy-associated EVs specifically induce cell death in certain immune cells, suggesting a role in maternal immune modulation.
Area of Science:
- Immunology
- Cell Biology
- Reproductive Biology
Background:
- Extracellular vesicles (EVs) are key mediators of intercellular communication.
- Circulating EVs are elevated during pregnancy, but their specific roles and characteristics remain unclear.
- Understanding pregnancy-related EV changes is crucial for deciphering maternal-fetal immune interactions.
Purpose of the Study:
- To investigate modifications in circulating EVs during pregnancy.
- To analyze changes in EV levels, markers, cytokine profiles, and their effects on peripheral blood cells.
- To clarify the immune-modulating functions of pregnancy-associated EVs.
Main Methods:
- Collected blood samples from 26 pregnant women (PW) and 59 non-pregnant women (NPW).
- Enriched EVs using ExoQuick™ or ultracentrifugation.
- Characterized EVs via nanoparticle tracking analysis, Western Blotting, and ELISA for cytokines (IFN-γ, IL-10, TGF-β1).
- Assessed EV uptake by peripheral blood cells and their function (caspase-3 activity) using imaging flow cytometry and flow cytometry.
Main Results:
- Circulating EVs were significantly increased in PW compared to NPW.
- EVs from PW showed elevated levels of immunosuppressive cytokines TGF-β1 and IL-10, even after normalization.
- EVs from both groups were taken up by NK cells, but only EVs from PW induced significant caspase-3 activity in CD56(dim) NK cells.
Conclusions:
- Pregnancy is associated with quantitative and qualitative alterations in circulating EVs.
- Increased immunosuppressive cytokines in pregnancy-associated EVs suggest a role in modulating the maternal immune response.
- These findings provide initial evidence for the immune-regulatory function of circulating EVs during pregnancy.
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