Etiology of Ulcerative Colitis—Autoimmunity and Immunoregulatory Abnormalities
Immunoregulatory abnormalities are thought to play a significant role in susceptibility for inflammatory bowel disease (IBD). In the healthy gut, antigens with the potential to induce inflammation are tolerated without inciting the inflammatory process. In patients with IBD, defects in immune regulation lead to upregulation of the inflammatory response by cells within the mucosa leading to release of pro-inflammatory cytokines. Several theories exist regarding the pathogenesis: dysfunctional response to normal luminal contents, infection, and defective mucosal barrier. The importance of host response to normal luminal contents is elucidated through animal studies involving the senescence-accelerated mouse P1 (SAMP1)/Yit mouse. This animal model spontaneously develops ileal inflammation under normal conditions. Matsumoto and colleagues investigated the effect of a sterile environment on development of disease in this mouse model. Animals raised in an environment that was "normal" (free from specific pathogens) and fed a sterilized diet spontaneously developed intestinal inflammation, while animals raised in a germ-free "sterile" environment did not develop inflammation. When introduced to a "normal" environment the germ-free animals developed inflammation. Furthermore, investigators noted that disease was less severe in the animals exposed to normal environment at a later age, suggesting that the timing of bacterial colonization is important to the progression of disease in this animal model.2603
The identification of autoantibodies associated with ulcerative colitis raises the question of whether the disease has an autoimmune component. Specifically, an autoimmune response directed toward mucin, goblet cells, colonocytes, or other cells has been postulated. Unfortunately, the specific role of autoimmunity and/or the identification of definitive autoantigens and the associated processes that lead to disease remain elusive.2604
Content on this page was last reviewed on October 31, 2009.
Content on this page was last changed on March 19, 2009.
References:| 2603. | Matsumoto S, Okabe Y, Setoyama H, et al. Inflammatory bowel disease-like enteritis and caecitis in a senescence accelerated mouse P1/Yit strain. Gut. 1998;43(1):71-78 . |
| 2604. | Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev. 2002;15(1):79-94 . |
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