Mice deficient in Th1-and Th2-type cytokines develop distinct forms of hapten-induced colitis
Mice deficient in Th1-and Th2-type cytokines develop distinct forms of hapten-induced colitis
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DOI：
10.1053/gast.2000.16500
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发表时间：
2000-09-01
期刊：
影响因子：
29.4
通讯作者：
McGhee, JR
中科院分区：
文献类型：
--
作者：
Dohi, T;Fujihashi, K;McGhee, JR
背景和目标：大多数小鼠炎症性肠病的实验模型与干扰素（IFN）-γ和其他促炎细胞因子的产生有关。我们假设，辅助性T细胞2（Th 2）型细胞也可能有助于结肠炎，并引起炎症不同于Th 1型细胞介导的。研究方法：与对照小鼠（C57 BL/6（+/+））相比，检查了白细胞介素（IL）-12 p40（IL-12（-/-））、IFN-γ（IFN-γ（-/-））或IL-4（IL-4（-/-））遗传缺陷的C57 BL/6背景小鼠中三硝基苯磺酸（TNBS）诱导的结肠炎。结果如下：C57 BL/6（+/+）、IFN-γ（-/-）和IL-12（-/-）小鼠出现结肠炎模式，其特征为隐窝变形、杯状细胞丢失和单核细胞浸润伴粘膜层纤维化，IL-4（-/-）小鼠由于穿透性溃疡而具有比其他组更高的死亡率;然而，幸存者出现了较轻的病变，仅限于局灶性急性溃疡，正常小鼠、IFN-gamma（-/-）小鼠或IL-12（-/-）小鼠的结肠CD 4（+）T细胞产生IL-4和IL-5。结论：在TNBS结肠炎中，Th 1样细胞因子应答诱导致命的、急性的、透壁的和局灶性类型的病变，而Th 2样细胞因子应答在该疾病晚期发生的隐窝和粘膜层的弥漫性萎缩性变化中起重要作用。
Background & Aims: Most experimental models for inflammatory bowel disease in mice are associated with production of interferon (IFN)-gamma and other proinflammatory cytokines. We hypothesized that T-helper 2 (Th2)-type cells could also contribute to the colitis and cause inflammation different than that mediated by Th1-type cells. Methods: Trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6 background mice genetically deficient in interleukin (IL)-12 p40 (IL-12(-/-)), IFN-gamma (IFN-gamma(-/-)), or IL-4 (IL-4(-/-)) was examined in comparison with control mice (C57BL/6(+/+)). Results: C57BL/6(+/+), IFN-gamma(-/-), and IL-12(-/-) mice developed patterns of colitis characterized by distortion of crypts, loss of goblet cells, and mononuclear cell infiltration with fibrosis of the mucosal layer, IL-4(-/-) mice had greater mortality than other groups because of penetrating ulcers; however, survivors developed milder lesions that were limited to focal acute ulceration, Colonic CD4(+) T cells from normal, IFN-gamma(-/-), or IL-12(-/-) mice produced both IL-4 and IL-5. Conclusions: In TNBS colitis, Th1-like cytokine responses induce fatal, acute, transmural, and focal types of lesions, whereas Th2-like cytokine responses play a significant role in the diffuse atrophic changes in crypts and the mucosal layer that occur in the late stages of this disease.