Inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the gastrointestinal tract and manifest mainly in two forms, Crohn’s disease (CD) and ulcerative colitis (UC). The currently accepted pathogenesis of IBD incorporates a close interplay between altered intestinal microbiota, reduced epithelial barrier function and aberrant mucosal immune reactions resulting in a disturbed intestinal homeostasis. Dysregulated T cell reactions against intestinal antigens are considered to be a causal or driving factor for IBD. However, technical limitations for the detection and characterization of microbiota-reactive T cells have so far prevented to determine the exact contribution of specific T cell subsets against individual microbes to the intestinal immune homeostasis and its dysregulation in IBD. In this project, we will use the antigen-reactive T cell enrichment (ARTE) technology, for highly sensitive in-depth characterization of human antigen-reactive T helper cell responses against candidate microbial antigens directly ex vivo in human blood or tissue.
We aim to understand how tolerance against certain microbial antigens is maintained in healthy humans and how it is disrupted in IBD patients. Analyzing the T cell-mediated contribution to intestinal inflammation, the quantitative and qualitative contribution of individual microbes to the local environment and the subsequent modulation of the T cell response in IBD patients will enable to answer important questions for the pathogenesis of IBD and for the development of improved diagnostics and therapeutics.