Dendritic cells in multiple sclerosis: key players in the immunopathogenesis, key players for new cellular immunotherapies?

Many studies have demonstrated the role of the adaptive immune system in the pathogenesis of multiple sclerosis (MS). Recent data suggest that dendritic cells (DCs), which are innate immune cells, also contribute to the pathogenesis of MS. In patients with MS, DCs are abundantly present in brain lesions, and display an altered phenotype and/or function as compared with this in healthy controls. DCs are thus in the position to pathologically influence the effector function of (auto-reactive) T and B cells. Interestingly, current first-line immunomodulating therapies for MS have been shown to restore DC phenotype and function, albeit in a non-specific manner. To date, clinical trials using agents specifically targeting DC function are ongoing. Moreover, several studies worldwide are currently investigating possible strategies to develop tolerogenic DCs. This review focuses on the phenotypic and functional alterations of conventional DCs and plasmacytoid DCs in patients with MS. Furthermore, we discuss how existing immunomodulating therapies for MS patients affect DC function and address future perspectives in the development of immunotherapies specifically targeting DCs.