Abstract
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.
Highlights
IntroductionMultiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS), leading to demyelination and axonal loss [1]
Six other women were under II line therapies, namely, natalizumab and fingolimog, and two of them continued the treatment throughout the first trimester
Pregnancy is a unique situation of physiological immunomodulation, as well as a strong
Summary
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS), leading to demyelination and axonal loss [1]. It is thought to arise from the interplay between genetic susceptibility and environmental exposure, which causes a breakdown of peripheral tolerance against CNS antigens [2]. MS is mainly driven by peripheral autoreactive CD4+ T lymphocytes, activated in the periphery and directed against CNS antigens. The reactivation of autoreactive T cells in the CNS triggers the recruitment and activation of additional immune cells to the areas of inflammation, the secretion of proinflammatory cytokines, chemokines and mediators, and the activation of resident microglia and astrocytes, which result in myelin damage [3]
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