Dissecting the involvement of toll-like receptors in the induction of IBD

Crohn's disease and ulcerative colitis are the major forms of inflammatory bowel disease (IBD). These diseases are characterized by chronic inflammations within the colon, and it is thought that intestinal bacteria may play a role in the pathogenesis of IBD. This is supported by genome scans within IBD patients, which have pointed towards the involvement of pathogen recognition receptors such as tolllike receptors (TLRs) in disease susceptibility. Furthermore, murine models of colitis exist that rely on immune responses against antigen specifically produced by genetically modified E. coli located within the colon (Iqbal, 2002). These findings support the hypothesis that intestinal flora may act as possible instigators or accomplices of these diseases via pathogen recognition receptors such as TLRs. To further clarify how TLRs may lead to the induction of colitis and how they could be facilitated by probiotics treatment, an antigen-specific model of colitis will be investigated that requires the adoptive transfer of antigenspecific CD4+ T cells in combination with intrarectal administration of antigen either expressed by bacteria, yeast, or in combination with specific individual TLR ligands. By dissecting the necessity of TLRs for the initiation and/or progression of intestinal inflammations, we may be able to develop drugs using TLRs as immunomodulatory targets.