Regulation of Intestinal Mucosal Immunity in a Mouse Model on Inflammatory Bowel Disease

白细胞介素-10基因缺陷型（IL-10 β-/-）小鼠自发地发展出肠道炎症，其特征在于整个胃肠道的多灶性病变，其与人类克罗恩病具有许多相似之处。在我们目前对该模型的研究中，我们阐明了肠上皮细胞凋亡在结肠炎症发生和发展中的作用。我们已经使用了人Bcl-2转基因小鼠，其中在IL-10^<-/->空白背景下，人Bcl-2（一种抗凋亡蛋白）在上皮细胞中表达，但在肠淋巴细胞中不表达。与非转基因IL-10%小鼠相比，Bcl-2转基因小鼠的肠上皮细胞凋亡较少，粘膜屏障维持良好，肠道炎症较少。Bcl-2没有改变浸润的肠淋巴细胞的细胞因子产生谱，但它减少了细胞的数量，可能导致炎症减少。提示上皮细胞凋亡是慢性肠道炎症的重要组成部分。可以考虑采取限制细胞凋亡的措施来预防或治疗此类疾病。

Interleukin-10 gene-deficient (IL-10^<-/->) mice spontaneously develop an intestinal inflammation characterized by multifocal lesions throughout the gastrointestinal tract, which has many similarities to human Crohn's disease. In our current study of this model we have elucidated the role of apoptosis in intestinal epithelial cells in the onset and development of the colonic inflammation. We have employed human Bcl-2 transgenic mice, in which human Bcl-2, an anti-apoptosis protein, was expressed in epithelial cells but not intestinal lymphocytes, on an IL-10^<-/-> null background. In comparison with the non-transgenic IL-10% mice, the Bcl-2 transgenic mice had less apoptosis of the intestinal epithelium, better-maintained mucosal barrier, and less intestinal inflammation. Bcl-2 did not alter the cytokine production profile of infiltrating intestinal lymphocytes, but it reduced the number of the cells, probably resulting in diminished inflammation. These results imply that epithelial cell apoptosis is an important component of disorders of chronic intestinal inflammation. Measures to limit the apoptosis might be considered for preventing or treating such conditions.