首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Intestinal overexpression of IL IL ‐18 promotes eosinophils‐mediated allergic disorders
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Intestinal overexpression of IL IL ‐18 promotes eosinophils‐mediated allergic disorders

机译:IL IL -18的肠道过表达促进嗜酸性粒细胞介导的过敏性疾病

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Summary Baseline eosinophils reside in the gastrointestinal tract; however, in several allergic disorders, excessive eosinophils accumulate in the blood as well in the tissues. Recently, we showed in?vitro that interleukin ( IL )‐18 matures and transforms IL ‐5‐generated eosinophils into the pathogenic eosinophils that are detected in human allergic diseases. To examine the role of local induction of IL ‐18 in promoting eosinophil‐associated intestinal disorders, we generated enterocyte IL ‐18‐overexpressing mice using the rat intestinal fatty acid‐binding promoter (Fabpi) and analysed tissue IL ‐18 overexpression and eosinophilia by performing real‐time polymerase chain reaction, Enzyme‐Linked Immunosorbent Assay and anti‐major basic protein immunostaining. Herein we show that Fabpi‐ IL ‐18 mice display highly induced IL ‐18 mRNA and protein in the jejunum. IL ‐18 overexpression in enterocytes promotes marked increases of eosinophils in the blood and jejunum. Our analysis shows IL ‐18 overexpression in the jejunum induces a specific population of CD 101 +? CD 274 + tissue eosinophils. Additionally, we observed comparable tissue eosinophilia in IL ‐13‐deficient‐Fabpi‐ IL ‐18 mice, and reduced numbers of tissue eosinophils in eotaxin‐deficient‐Fabpi‐ IL ‐18 and IL ‐5‐deficient‐Fabpi‐ IL ‐18 mice compared with Fabpi‐ IL ‐18 transgenic mice. Notably, jejunum eosinophilia in IL ‐5‐deficient‐Fabpi‐ IL‐ 18 mice is significantly induced compared with wild‐type mice, which indicates the direct role of induced IL ‐18 in the tissue accumulation of eosinophils and mast cells. Furthermore, we also found that overexpression of IL ‐18 in the intestine promotes eosinophil‐associated peanut‐induced allergic responses in mice. Taken together, we provide direct in?vivo evidence that induced expression of IL ‐18 in the enterocytes promotes eotaxin‐1, IL ‐5 and IL ‐13 independent intestinal eosinophilia, which signifies the clinical relevance of induced IL ‐18 in eosinophil‐associated gastrointestinal disorders (EGIDs) to food allergens.
机译:摘要基线嗜酸性粒细胞位于胃肠道;然而,在几种过敏性疾病中,过量的嗜酸性粒细胞在组织中也会积聚在血液中。最近,我们在白细胞介素(IL)-18的体外显示并将IL-5产生的嗜酸性粒细胞转化为在人体过敏性疾病中检测到的病原嗜酸性粒细胞。为了检查局部诱导IL -18在促进嗜酸性粒细胞相关肠梗理疾病方面的作用,我们使用大鼠肠脂肪酸结合启动子(FABPI)产生肠细胞IL -18-过度抑制小鼠,并分析组织IL -18过表达和嗜酸性粒细胞进行实时聚合酶链反应,酶联免疫吸附测定和抗重型碱性免疫染色。在此,我们表明Fabpi-IL -18小鼠在Jejunum中显示出高度诱导的IL -18 mRNA和蛋白质。 IL -18肠细胞的过表达促进血液和jejunum中标记的嗜酸性粒细胞增加。我们的分析显示了Jejunum中的IL -18过表达诱导了CD 101 +的特定群体? CD 274 +组织嗜酸性粒细胞。此外,我们观察到IL -13缺陷型 - Fabpi-IL -18小鼠中的可比较的组织嗜酸性粒细胞,以及在肠蛋白缺乏 - Fabpi-IL-18和IL-5缺陷的植物中的组织嗜酸性粒细胞的数量减少与Fabpi-IL -18转基因小鼠相比。值得注意的是,与野生型小鼠相比,IL -5缺陷型杂草-18-18小鼠中的Jejunum嗜酸性粒细胞显着诱导,这表明诱导IL -18在嗜酸性粒细胞和肥大细胞的组织积累中的直接作用。此外,我们还发现,肠道IL -18的过度表达促进了嗜酸性粒细胞相关的花生诱导的小鼠的过敏反应。我们一起服用,提供了直接的?体内证据,其诱导肠细胞中IL -18的表达促进ETOXIN-1,IL-5和IL -13独立肠嗜酸性粒细胞粒细胞粒细胞粒细胞染率,这意味着诱导IL -18在嗜酸性粒细胞相关的临床相关性胃肠疾病(Egids)食品过敏原。

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