Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa

被引:172
|
作者
Watanabe, M
Ueno, Y
Yajima, T
Okamoto, S
Hayashi, T
Yamazaki, M
Iwao, Y
Ishii, H
Habu, S
Uehira, M
Nishimoto, H
Ishikawa, H
Hata, J
Hibi, T
机构
[1] Keio Canc Ctr, Shinjuku Ku, Tokyo 160, Japan
[2] Keio Univ, Sch Med, Dept Internal Med, Tokyo 160, Japan
[3] Keio Univ, Sch Med, Dept Microbiol, Tokyo 160, Japan
[4] Keio Univ, Sch Med, Dept Pathol, Tokyo 160, Japan
[5] Tokai Univ, Sch Med, Dept Immunol, Isehara, Kanagawa 25911, Japan
[6] Shionogi Inst Med Sci, Osaka 553, Japan
来源
JOURNAL OF EXPERIMENTAL MEDICINE | 1998年 / 187卷 / 03期
关键词
D O I
10.1084/jem.187.3.389
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we report that transgenic mice expressing murine IL-7 cDNA driver by the SR alpha promoter developed chronic colitis in concert with the expression of SR alpha/IL-7 transgene in the colonic mucosa. IL-7 transgenic but not littermate mice developed chronic colitis at 4-12 wk of age, with histopathological similarity to ulcerative colitis in humans. Southern blot hybridization and competitive PCR demonstrated that the expression of IL-7 messenger RNA was increased in the colonic mucosal lymphocytes but not in the colonic epithelial cells. IL-7 protein accumulation was decreased in the goblet cell-depleted colonic epithelium in the transgenic mice. Immunohistochemical and cytokine production analysis showed that lymphoid infiltrates in the lamina propria were dominated by T helper cell, type 1 CD4(+) T cells. Flow cytometric analysis demonstrated that CD4(+) intraepithelial T cells were increased, but T cell receptor gamma/delta T cells and CD8 alpha/alpha. cells were not increased in the area of chronic inflammation. Increased IL-7 receptor expression in mucosal lymphocytes was demonstrated in the transgenic mice. These findings suggest that chronic inflammation in the colonic mucosa may be mediated by dysregulation of colonic epithelial cell-derived IL-7, and this murine model of chronic colitis may contribute to the understanding of the pathogenesis of human inflammatory bowel disease.
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收藏
页码:389 / 402
页数:14
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