GCOE global education seminar“Of mice and men – how research in dendritic cells exposes immunopathogenesis of autoimmune disease”

Activity of the RelB subunit of NF-kappaB underlies the capacity of dendritic cells (DCs) to stimulate T cells. Inflammatory microbial or T cell-derived signals induce the nuclear translocation and transcriptional activity of RelB to the nucleus of DCs. In response to lipopolysaccharide or CD40L, RelB-deficient DCs demonstrate impaired induction of MHC class II and costimulation that are required for productive TCR signaling and effective T cell priming. Moreover, antigen-exposed RelB-deficient DCs induce antigen-specific tolerance; in contrast to antigen-exposed DCs, which promote immunity. Paradoxically, RelB-deficient mice develop spontaneous Th2 T-cell-dependent multi-system autoimmune and allergic disease. I will discuss the mechanisms of tolerance and autoimmunity in these settings, and how we are exploiting this to understand and treat human autoimmune disease.