Project B05
In situ reprogramming of dendritic cells for immunomodulation of CNS-specific Foxp3+ regulatory T cells
Background
It has been reported that in MS patients there is an imbalance between Treg cells and effector T cells, while Treg cells were shown to be reduced and additionally have a less suppressive activity. We could earlier show that application of a noninflammatory mRNA encoding a CNS-specific antigen nearly completely protects from CNS autoimmunity in a mouse model of MS, which went in line with increased frequencies of Treg cells in the spleen.
We hypothesize that modulation of Treg cell populations through vaccination with a noninflammatory mRNA encoding a CNS-specific antigen has a therapeutic implication for MS patients.
Strategy
In this project we investigate in more detail the impact of in situ reprogrammed immature dendritic cells (iDCs) on the generation of CNS-specific Foxp3+ Treg cells. To this end, we apply noninflammatory mRNA encoding MS-specific antigens for transient in vivo reprogramming of splenic iDCs in mouse models of MS. This allows us to define the site of tolerance induction by tracking the migration of photoconverted Teff/Treg cells and to characterize the expression profile of both iDCs and T cells in-depth. We will further explore the impact of noninflammatory mRNA vaccination on B cell responses in B cell dependent EAE models.