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.

Transgenic mice were created in which IL-10 is expressed by the intestinal epithelial cells.

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 β 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.

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.