Insights into the pathogenesis of inflammatory bowel diseases provided by new rodent models of spontaneous colitis

作者：Ryan Balfour Sartor · 发表于：Inflammatory Bowel Diseases · 年份：1995 · DOI：10.1002/ibd.3780010108 · 被引用次数：54 · 研究领域：Inflammatory Bowel Disease、Digestive system and related health、Gastrointestinal motility and disorders

New molecular techniques that permit overexpression or deletion of targeted genes have created a new class of rodent models of intestinal inflammation. Spontaneous colitis, with variable small bowel, duodenal, and systemic inflammation, develops in transgenic HLA-B27/β2-microglobulin rats; interleukin-2, interleukin-10, transforming growth factor-β1, T cell receptor, and G protein deficient (knockout) mice; the new C3H/HeJ Bir mouse substrain; following transfer of CD45RBhigh lymphocytes into immunodeficient mice; and following bone marrow transplantation into cyclosporin A-treated mice. These models provide the following important insights into the mechanisms of chronic intestinal inflammation: (a) Ubiquitous luminal bacteria have a critical role in induction and perpetuation of chronic intestinal and systemic inflammation in genetically susceptible hosts. (b) Defective immunoregulation, especially immunosuppression, can lead to chronic colitis. (c) Alteration of any of a number of immunoregulatory molecules can induce almost identical phenotypes of intestinal inflammation. (d) Host genetic susceptibility determines the incidence and aggressiveness of disease. (e) The immune system, especially immunoregulatory T lymphocytes, mediates chronic colitis. Results in these models are consistent with the hypothesis that chronic intestinal and related systemic manifestations are the result of an inappropriately aggressive immune response to ubiquitous luminal bacterial constituents,...