A novel model of appendicitis and appendectomy to investigate inflammatory bowel disease pathogenesis and remediation

The appendix contains copious lymphoid tissue and is constantly exposed to gut flora. Appendicitis and appendectomy (AA) has been shown to prevent or significantly ameliorate ulcerative colitis. In our novel murine AA model, the only existing experimental model of AA, the appendiceal pathology closely resembles that of human appendicitis; and AA offers an age-, bacteria- and antigen-dependent protection against colitis. Appendicitis and appendectomy performed in the most proximal colon curbs T helper 17 cell activity, curtails autophagy, modulates interferon activity-associated molecules, and suppresses endothelin vasoactivity-mediated immunopathology/vascular remodelling in the most distal colon. These AA-induced changes contribute to the limitation/amelioration of colitis pathology. Investigating strategies to manipulate and modulate different aspects of these pathways (using monoclonal antibodies, combinatorial peptides, and small molecules) would offer novel insight into inflammatory bowel disease pathogenesis, and will augment the development of new therapeutic options to manage recalcitrant colitis.