Project A09
CK2 as a molecular switch regulating immunity and tolerance by APC-dependent induction of Treg cells
Background
The fragile balance between immunity and tolerance in the gastrointestinal tract is accomplished by the gut-associated lymphoid tissue (GALT) and dysbalanced induction of proinflammatory T cell subsets and Treg cells contributes to the development of inflammatory bowel disease (IBD) and central nervous system autoimmunity. Polarization and differentiation of these T cells is steered by a heterogeneous family of myeloid antigen-presenting cells (APC) and we earlier identified CK2 to be crucially involved in orchestrating immunity and tolerance in the GALT.
We hypothesize that microbiota-derived metabolites control the activity of CK2 in APC and thereby modulate the induction of Treg cells.
Strategy
We aim at identifying microbiota- and diet-derived factors regulating CK2-dependent Treg cell induction by characterizing the effect of selected natural polyamines on dendritic cells (DCs) and Treg cell activation in vitro and in vivo. We further dissect the impact of CK2 in DCs on intracellular signal transduction pathways and regulation of gene expression.