Regulation of mucosal immune responses by recombinant interleukin 10 produced by intestinal epithelial cells in mice
Regulation of mucosal immune responses by recombinant interleukin 10 produced by intestinal epithelial cells in mice
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DOI：
10.1053/gast.2002.33655
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发表时间：
2002-06-01
期刊：
影响因子：
29.4
通讯作者：
Cheroutre, H
中科院分区：
文献类型：
--
作者：
De Winter, H;Elewaut, D;Cheroutre, H
背景和目的：白细胞介素 (IL)-10 是一种具有抗炎特性的细胞因子。本研究的目的是探讨 IL-10 的位点特异性递送对肠道免疫反应的影响。方法：创建转基因小鼠，其中肠上皮细胞表达 IL-10。结果：转基因小鼠小肠上皮内淋巴细胞数量显着增加。转基因动物的粘膜淋巴细胞产生的 1 型辅助 T 细胞因子比野生型淋巴细胞少。相比之下，转化生长因子13的产量增加。此外，转基因小鼠的上皮层CD4(+)CD25(+) T细胞显着富集。此外，转基因小鼠小肠中产生免疫球蛋白 A 的 B 细胞数量增加。这些影响是局部的，因为脾淋巴细胞不受影响。炎症性肠病模型研究表明，转基因IL-10能够减轻右旋糖酐硫酸钠给药或CD4(+)CD45RB(high)脾细胞过继转移诱导的急性结肠炎，对IL-10(-/-)小鼠自发产生的慢性肠道炎症有一定作用。结论：这些观察结果为体内淋巴上皮串扰提供了证据，通过这种串扰，上皮细胞局部产生的细胞因子可以调节肠道内的免疫反应，而无需进行全身性改变。
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 epithelia[ 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 13 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.