Towards a ready-to-use MS treatment: the use of tolerogenic dendritic cells (tolDC) in the treatment of MS is currently being investigated. TolDCs are able to modulate the immune response and (re)establish self-tolerance. However, the mechanism of function of these cells is not yet fully understood. In this project, we will study the role of extracellular vesicles (EVs) in modulating the immune response via tolDCs.

EVs are membrane vesicles produced by almost all cells and play a role in immune regulation. In particular, the cargo of EVs can affect the immune response.  Given the increasing evidence for the role of cellular metabolism in immune cell function as well as our preliminary data, which show an altered metabolome and lipidome of tolDC, we believe that EVs are involved in the mechanism of action of tolDC. Therefore, we will investigate the immunosuppressive properties of tolDC-derived EVs and their ability to induce tolerance. This would contribute to a better understanding of tolDCs and their mechanism of action. These results could also lead to the development of a cell-free therapy for MS that would avoid the drawbacks of cell-based therapies. Multiple sclerosis (MS) is a complex neurodegenerative disease of the central nervous system (CNS) that currently affects about 15,000 people in Belgium. To date, there is still no cure for MS, but several immunomodifying treatments have been developed. The use of tolerogenic dendritic cells (tolDC) in the treatment of MS is currently under investigation. These tolDCs are able to modulate the immune response and (re)establish self-tolerance. However, their exact mechanism of action has not yet been fully elucidated. In this project, we hypothesise that tolDCs modulate the autoreactive response via extracellular vesicles (EVs). EVs are nanosized membrane vesicles that are released by almost all cell types and have been found to be involved in immune regulation. In particular, the cargo carried by these EVs is able to influence the immune response. The growing evidence for the role of metabolism in immune cell differentiation and function, as well as our preliminary data, which indicate an altered metabolome and lipidome of tolDCs, we anticipate that metabolite-containing EVs play a role in the mode of action of tolDCs. Therefore, we are interested in investigating the immunosuppressive properties of tolDC-derived EVs and their ability to induce tolerance. This research would lead to a better understanding of the mechanism of action of tolDC. Furthermore, the results could lead to the development of a cell-free therapy for MS that would avoid the drawbacks associated with cell therapy.