MECHANISMS OF IMMUNE CELL-MEDIATED TISSUE-INJURY IN INFLAMMATORY BOWEL-DISEASE (REVIEW)

This review discusses the mechanisms and pathways of immune cell-media ted intestinal inflammation and tissue injury in inflammatory bowel di sease (IBD). Our lack of understanding of how the mucosal immune syste m normally functions to maintain the balance between tolerance and imm unity to innumerable dietary and bacterial constituents of the gut is perhaps the biggest obstacle to understanding the cause(s) of IBD, and to developing more effective treatments for these debilitating disord ers. Evidence that abnormalities or disruptions in the interaction of immune cells and gut bacteria can trigger or contribute to changes in the composition, regulation and activity of the mucosal immune system that result in inflammatory immune responses and tissue injury are dis cussed. Based upon these studies, we propose a model to explain how a breakdown in regulation and failure to resolve immune responses in the gut mucosa results in persistent activation of T lymphocytes and othe r immune cells and the uncontrolled production of soluble inflammatory mediators that directly or indirectly produce the pathophysiological changes and tissue injury characteristic of IBD.