A First Phenotypic and Functional Characterization of Placental Extracellular Vesicles from Women with Multiple Sclerosis

• Published in: International journal of molecular sciences Vol. 22; no. 6; p. 2875
• Main Authors: Martire, Serena, Montarolo, Francesca, Spadaro, Michela, Perga, Simona, Sforza, Maria Ludovica, Marozio, Luca, Frezet, Federica, Bruno, Stefania, Chiabotto, Giulia, Deregibus, Maria Chiara, Camussi, Giovanni, Botta, Giovanni, Benedetto, Chiara, Bertolotto, Antonio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-03-2021; MDPI
• Subjects: Antigens; CD14 antigen; CD4 antigen; Cell Communication - genetics; Cell proliferation; Coculture Techniques; Cytokines; Cytokines - genetics; Decidua; Decidua - immunology; Decidua - metabolism; Extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - immunology; Female; Fetuses; Gestational age; Humans; Immune system; Immunity - genetics; Immunomodulation; Immunomodulation - genetics; Inflammation; Lymphocytes; Lymphocytes T; Monocytes; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Physiology; Placenta; Placenta - immunology; Placenta - metabolism; Pregnancy; Progenitor cells; Proteome - genetics; Remission; Stem cells; Surface markers; T-Lymphocytes, Regulatory - immunology; trophoblast; Trophoblasts - immunology; Trophoblasts - metabolism; Vesicles; Womens health; placenta; extracellular vesicles; trophoblast; decidua; multiple sclerosis; pregnancy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22062875

Pregnancy is a unique situation of physiological immunomodulation, as well as a strong Multiple Sclerosis (MS) disease modulator whose mechanisms are still unclear. Both maternal (decidua) and fetal (trophoblast) placental cells secrete extracellular vesicles (EVs), which are known to mediate cellular communication and modulate the maternal immune response. Their contribution to the MS disease course during pregnancy, however, is unexplored. Here, we provide a first phenotypic and functional characterization of EVs isolated from cultures of term placenta samples of women with MS, differentiating between decidua and trophoblast. In particular, we analyzed the expression profile of 37 surface proteins and tested the functional role of placental EVs on mono-cultures of CD14
monocytes and co-cultures of CD4
T and regulatory T (Treg) cells. Results indicated that placental EVs are enriched for surface markers typical of stem/progenitor cells, and that conditioning with EVs from samples of women with MS is associated to a moderate decrease in the expression of proinflammatory cytokines by activated monocytes and in the proliferation rate of activated T cells co-cultured with Tregs. Overall, our findings suggest an immunomodulatory potential of placental EVs from women with MS and set the stage for a promising research field aiming at elucidating their role in MS remission.