The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor α mutant mice
The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor α mutant mice
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DOI：
10.1016/s0016-5085(99)70128-9
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发表时间：
1999-02-01
期刊：
影响因子：
29.4
通讯作者：
Bhan, AK
中科院分区：
文献类型：
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作者：
Mizoguchi, A;Mizoguchi, E;Bhan, AK
背景与目的：T细胞受体或突变(TCRα(-/-))小鼠自发发生类似溃疡性结肠炎(UC)的结肠炎。通过建立IL-4或干扰素-γ缺陷的TCRα(-/-)小鼠，研究IL-4和干扰素-γ在结肠炎发病机制中的作用。方法：将TCRα(-/-)小鼠与IL-4或干扰素-γ缺陷小鼠杂交，建立双突变小鼠。在6个月龄时对结肠炎进行大体和组织学评估，并分析这些小鼠肠系膜淋巴和结肠中的细胞因子谱。结果：IL-4的缺乏显著抑制了6个月龄小鼠结肠炎的发生。相比之下，干扰素-伽马(-/-)x TCRα(-/-)小鼠发生结肠炎的情况与TCRα(-/-)小鼠相似。此外，与IL-4(-/-)x TCRα(-/-)小鼠相比，TCRα(-/-)小鼠和干扰素-γ(-/-)×TCRα(-/-)小鼠的结肠上皮细胞增殖明显增强。持续给予重组IL-4可促进IL-4(-/-)x TCRα(-/-)小鼠结肠上皮细胞的增殖。结论：IL-4在TCRα(-/-)小鼠结肠炎的发生发展中起重要作用。相反，在缺乏干扰素-γ的情况下，TCRα(-/-)小鼠可能会发生严重的结肠炎。
Background & Aims: T-cell receptor or mutant (TCR alpha(-/-)) mice spontaneously develop colitis resembling ulcerative colitis (UC). The role of interleukin (IL)-4 and interferon (IFN)-gamma in the pathogenesis of colitis was examined by creating IL-4- or IFN-gamma-deficient TCR alpha(-/-) mice. Methods: Double-mutant mice were created by crossing TCR alpha(-/-) mice with IL-4- or IFN-gamma-deficient mice. Colitis was grossly and histologically assessed at 6 months of age, and the cytokine profile in the mesenteric lymph nodes and colons in these mice was analyzed. Results: The lack of IL-4 dramatically suppressed the development of colitis at 6 months of age. In contrast, IFN-gamma(-/-) x TCR alpha(-/-) mice developed colitis similar to that present in TCR alpha(-/-) mice. Furthermore, proliferation of colonic epithelial cells was markedly increased in TCR alpha(-/-) mice and IFN-gamma(-/-) x TCR alpha(-/-) mice compared with IL-4(-/-) x TCR alpha(-/-) mice. Continuous administration of recombinant IL-4 led to increased colonic epithelial cell proliferation in IL-4(-/-) x TCR alpha(-/-) mice. Conclusions: IL-4 plays an important role in the development of colitis in TCR alpha(-/-) mice. In contrast, severe colitis in TCR alpha(-/-) mice can develop in the absence of IFN-gamma.