Abstract
Multiple Sclerosis is a complex neurodegenerative disease of the central nervous system (CNS), currently affecting almost 15 000 people in Belgium. To date, there is still no cure for MS, but several immune-modifying treatments have been developed. The use of tolerogenic dendritic cells (tolDC) for the treatment of MS is currently being investigated. These tolDC can modulate the immune response and (re)establish self-tolerance. However, their exact working mechanism has not been fully elucidated yet. In this project, we hypothesize that tolDC modulate the auto-reactive response via extracellular vesicles (EV). EV are nanosized membrane vesicles that are released by almost every cell type and have been reported to be involved in immune regulation. In particular, the cargo carried by these EV can influence the immune response. Indeed, the cargo compromising of functionally active compounds such as RNAs, lipids, metabolites, and proteins can alter the phenotypic and functional properties of the recipient cells. Hence, we anticipate a role of immunomodulatory cargo-containing EVs in the mode-of-action of tolDC. For this, we aim to explore the immunosuppressive properties of tolDC-derived EV and their capacity to establish tolerance. This research would contribute to a better understanding of the working mechanism of tolDC. In addition, results could lead to the development of a cell-free therapy for MS surpassing the drawbacks associated with cell therapy.
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