Recent advances in genetic engineering techniques have made possible new and exciting approaches to generating models of inflammatory bowel disease in mice and rats. Several recent studies have demonstrated that targeted deletions of genes encoding for interleukin-2, interleukin-10, or certain T-cell receptor proteins produce mice that spontaneously develop chronic intestinal inflammation similar to human inflammatory bowel disease. In addition, it has been demonstrated that the introduction of HLA-B27 and human β2-microglobulin genes into rats produces transgenic animals that spontaneously develop chronic gastrointestinal inflammation. Data derived from these studies suggest that T cells play an important role in regulating B-cell activity, such that an unrestrained or unregulated B-cell response to normal luminal antigens or bacterial products promotes chronic gut inflammation. In addition, these studies demonstrate that endogenous luminal bacteria are important in promoting or exacerbating chronic gut inflammation. Indeed, these studies indicate that the production of very different defects in the immune system leads, in many cases, only to gut mucosal inflammation, suggesting that the gut mucosa is subjected to substantially more antigenic “stress” than are other tissues. Thus, these new models offer new and exciting avenues of research for the study of the pathogenesis of inflammatory bowel disease as well as providing new and possibly more appropriate models for the development and testing of new therapeutic agents for the treatment of these diseases.
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