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

Mamoru Watanabe, Yoshitaka Ueno, Tomoharu Yajima, Susumu Okamoto, Tatsuhiko Hayashi, Motomi Yamazaki, Yasushi Iwao, Hiromasa Ishii, Sonoko Habu, Masahiro Uehira, Hirofumi Nishimoto, Hiromichi Ishikawa, Jun Ichi Hata, Toshifumi Hibi

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183 Citations (Scopus)

Abstract

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 SRα promoter developed chronic colitis in concert with the expression of SRα/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 γ/δ T cells and CD8α/α 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.

Original languageEnglish
Pages (from-to)389-402
Number of pages14
JournalJournal of Experimental Medicine
Volume187
Issue number3
DOIs
Publication statusPublished - 1998 Feb 2

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Interleukin-7
Colitis
Transgenic Mice
Mucous Membrane
Proteins
Interleukin-7 Receptors
Lymphocytes
Epithelial Cells
T-Lymphocytes
Inflammation
Th1 Cells
Goblet Cells
T-Cell Antigen Receptor
Southern Blotting
Transgenes
Ulcerative Colitis
Inflammatory Bowel Diseases
Epithelium
Complementary DNA
Cytokines

ASJC Scopus subject areas

  • Immunology

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Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa. / Watanabe, Mamoru; Ueno, Yoshitaka; Yajima, Tomoharu; Okamoto, Susumu; Hayashi, Tatsuhiko; Yamazaki, Motomi; Iwao, Yasushi; Ishii, Hiromasa; Habu, Sonoko; Uehira, Masahiro; Nishimoto, Hirofumi; Ishikawa, Hiromichi; Hata, Jun Ichi; Hibi, Toshifumi.

In: Journal of Experimental Medicine, Vol. 187, No. 3, 02.02.1998, p. 389-402.

Research output: Contribution to journalArticle

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, JI & Hibi, T 1998, 'Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa', Journal of Experimental Medicine, vol. 187, no. 3, pp. 389-402. https://doi.org/10.1084/jem.187.3.389
Watanabe, Mamoru ; Ueno, Yoshitaka ; Yajima, Tomoharu ; Okamoto, Susumu ; Hayashi, Tatsuhiko ; Yamazaki, Motomi ; Iwao, Yasushi ; Ishii, Hiromasa ; Habu, Sonoko ; Uehira, Masahiro ; Nishimoto, Hirofumi ; Ishikawa, Hiromichi ; Hata, Jun Ichi ; Hibi, Toshifumi. / Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa. In: Journal of Experimental Medicine. 1998 ; Vol. 187, No. 3. pp. 389-402.
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