Nakajima-Adachi Haruyo, Ebihara Ayumi, Kikuchi Akira, Ishida Tsuyoshi, Sasaki Kiyomi, Hirano Kiyomi, Watanabe Hiroko, Asai Kazumi, Takahashi Yoshimasa, Kanamori Yutaka, Shimojo Naoki, Matsuda Hiroshi, Kohno Yoichi, Hachimura Satoshi, Kaminogawa Shuichi
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi, Japan.
J Allergy Clin Immunol. 2006 May;117(5):1125-32. doi: 10.1016/j.jaci.2006.01.016.
Clarification of the mechanisms underlying the development of food-sensitive intestinal inflammation will provide an important clue to combating food allergies.
To establish a model of intestinal inflammation caused by oral administration of antigen without additional treatments, we focused on the ovalbumin (OVA) 23-3 T-cell receptor transgenic mouse, which had been reported to have high serum antigen-specific IgE responses to the feeding of an egg white diet.
Changes in body weight of mice fed an egg white diet were monitored throughout the 28-day experimental period. After the 28-day feeding, intestinal tissues were harvested for histologic examination. Endogenous production of cytokines and histamine in the jejunum, and production of cytokines secreted by OVA-specific CD4+ T cells purified from mesenteric lymph nodes, were analyzed.
Egg white diet-fed OVA23-3 mice developed weight loss and inflammation with villous atrophy and goblet cell hyperplasia, especially in the jejunum. A further characteristic feature was evidence of weight recovery and tissue repair. Jejunal inflammation was also observed in egg white diet-fed recombination activating gene (RAG)-2-deficient OVA23-3 mice. In addition, tissue sections revealed significant infiltration of specific IgE-positive cells and IgE-positive degranulating mast cells. Higher levels of IL-4 and significant levels of histamine were detected in the tissues. In the supernatant of OVA-stimulated T cells, IL-10 levels were also markedly elevated.
We report that high-dose and continuous intake of primitive OVA alone induces enteropathy containing regions under repair in OVA23-3 mice. Antigen-specific T cells and inflammatory cells primed by T(H)2 responses play important roles in regulation of development and improvement of the disease.
Long-term antigen intake causes T(H)2-dependent and food-sensitive enteropathy followed by tissue repair.
阐明食物敏感性肠道炎症发生发展的机制将为对抗食物过敏提供重要线索。
为建立无需额外处理经口服抗原诱导的肠道炎症模型，我们聚焦于卵清蛋白（OVA）23 - 3 T细胞受体转基因小鼠，据报道该小鼠对喂食蛋清饮食有高血清抗原特异性IgE反应。
在整个28天的实验期内监测喂食蛋清饮食小鼠的体重变化。28天喂食后，采集肠道组织进行组织学检查。分析空肠中细胞因子和组胺的内源性产生，以及从肠系膜淋巴结纯化的OVA特异性CD4 + T细胞分泌的细胞因子产生情况。
喂食蛋清饮食的OVA23 - 3小鼠出现体重减轻和炎症，伴有绒毛萎缩和杯状细胞增生，尤其是在空肠。另一个特征是体重恢复和组织修复的证据。在喂食蛋清饮食的重组激活基因（RAG）- 2缺陷型OVA23 - 3小鼠中也观察到空肠炎症。此外，组织切片显示特异性IgE阳性细胞和IgE阳性脱颗粒肥大细胞有显著浸润。在组织中检测到较高水平的IL - 4和显著水平的组胺。在OVA刺激的T细胞上清液中，IL - 10水平也明显升高。
我们报道，单独高剂量持续摄入天然OVA可诱导OVA23 - 3小鼠出现包含修复区域的肠病。由T（H）2反应引发的抗原特异性T细胞和炎性细胞在疾病的发生发展和改善调节中起重要作用。
长期摄入抗原会导致T（H）2依赖性和食物敏感性肠病，随后是组织修复。
