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Publication : Regulation of mucosal immune responses by recombinant interleukin 10 produced by intestinal epithelial cells in mice.

First Author  De Winter H Year  2002
Journal  Gastroenterology Volume  122
Issue  7 Pages  1829-41
PubMed ID  12055591 Mgi Jnum  J:77046
Mgi Id  MGI:2180937 Doi  10.1053/gast.2002.33655
Citation  De Winter H, et al. (2002) Regulation of mucosal immune responses by recombinant interleukin 10 produced by intestinal epithelial cells in mice. Gastroenterology 122(7):1829-41
abstractText  BACKGROUND & AIMS: Interleukin (IL)-10 is a cytokine with anti-inflammatory properties. The aim of this study was to explore the effect of a site-specific delivery of IL-10 on intestinal immune responses. METHODS: Transgenic mice were created in which IL-10 is expressed by the intestinal epithelial cells. RESULTS: Transgenic mice showed a marked increase in the number of intraepithelial lymphocytes in the small intestine. Mucosal lymphocytes of transgenic animals produced fewer T helper type 1 cytokines than wild-type lymphocytes. By contrast, the production of transforming growth factor beta was increased. Moreover, the epithelial layer in transgenic mice was significantly enriched for CD4(+)CD25(+) T cells. Furthermore, transgenic mice had increased numbers of immunoglobulin A-producing B cells in the small intestine. These effects were local because splenic lymphocytes were not affected. Studies in models of inflammatory bowel disease showed that transgenic IL-10 was able to attenuate the acute colitis induced by dextran sodium sulfate administration or by adoptive transfer of CD4(+)CD45RB(high) splenocytes, with a modest effect on the chronic intestinal inflammation arising spontaneously in IL-10(-/-) mice. CONCLUSIONS: These observations provide evidence for an in vivo lymphoepithelial cross talk, by which cytokines locally produced by epithelial cells can regulate immune responses in the intestine without systemic modifications.
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