Exploring inhibitors and vitamins to generate tolerogenic dendritic cells for Multiple Sclerosis

Abstract

Not only are dendritic cells (DC) the main inducers of a primary T cell response, they also determine the profile of that response. This makes DC interesting immune modulating agents. In Multiple Sclerosis (MS), tolerogenic DC could be used to restore tolerance. To date, there is no consensus concerning the stimuli that produce that type of DC. We therefore hypothesized that treatment of DC with specific stimuli generates tolerogenic DC able to restore the immune balance in EAE mice, an MS animal model. In this study, 3 stimuli were compared. Treatment of immature DC with SAHA produced semi-mature DC after LPS challenge, with reduced expression of co-stimulatory molecules and decreased secretion of pro-inflammatory cytokines. Bone marrow treatment with active vitamin D3 also lowered co-stimulatory molecule expression. Treatment of EAE mice with Captopril-treated DC was insufficient to block EAE development. We conclude that SAHA is the stimulus with the most DC tolerizing potential.