ESTABLISHMENT OF NOVEL EXPERIMENTAL SYSTEM(S) FOR EVALUATION OF THE IMMUNE FUNCTION OF FOOD COMPONENTS USING CELLS FROM THE INTESTINAL IMMUNE SYSTEM

建立利用肠道免疫系统细胞评估食品成分免疫功能的新型实验系统

• 批准号: 11556023
• 负责人: KAMINOGAWA Shuichi
• 金额: $ 8.45万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11556023/
• 关键词: food; immune function; nucleotide; interleukin 7; intestional epithelial cell; ATBC; IgA; allergy; 腸管免疫系; 化学物質; 経口免疫寛容; 小腸上皮; T細胞; 腸管; サイトカイン

1. Analysis of intestinal immune system. (1) Feeding OVA diet to OVA-specific T cell receptor transgenic (TCR-Tg) mice enhanced interleukin (IL)-5 and IL-6 secretion of lamina propria lymphocytes. Feeding of OVA diet to these TCR tg mice also resulted in allergic reactions in the small intestine, suggesting its usefulness as an animal model for gastrointestinal food allergy^* We found that when Peyer's patch dendritic cells were added to cultures containing OVA, TCR-TG T cells and B cells, the secretion of IgA was induced.2. Examination of the immune function of food components using cells from the intestinal immune system, (1) ,Effect of dietary nucleotides on the response of gut-associated lymphoid tissue was investigated. The proportion of T-cell receptor (TCR) γ0 intraepithelial lymphocytes (IEL) in BALB/c mice fed a diet supplemented with nucleotides (NT(+) diet) was significantly higher than that in mice fed the nucleotide-free control diet. Intestinal epithelial cells (IEC) from NT(+) diet-fed mice produced higher levels of interlocking (IL-) 7 and TGF-β, which are important in the development of TORγδo^+ IEL and in IgA responses, respectively, than those from control diet-fed mice. When nucleotides were added to a primary culture of mouse IEC, secretion of EL-7, but not that of TGF-β, was increased. These results demonstrate that nucleotides can modify directly the secretion of IL-7 from IEC, and; suggest that the mechanisms underlying the increased secretion of IL-7 from IEC in mice fed the NT(+) diet were different from those for the increased secretion of TGF-β. (2) Oral administration of acetyl tributyl citrate (ATBC), which is a plasticizer used in food containers, affected the histamine content of the intestine of OVA-fed TCR-Tg mice, suggesting that ATBC modified allegic reactions in the intestine.

1. 肠道免疫系统分析。(1) OVA特异性T细胞受体转基因（TCR-Tg）小鼠饲喂OVA日粮可增强固有层淋巴细胞白细胞介素(IL)-5和IL-6的分泌。给这些TCR- tg小鼠喂食OVA饲料也会引起小肠过敏反应，提示其可作为胃肠道食物过敏的动物模型^*我们发现，当将Peyer's patch树突状细胞添加到含有OVA、TCR- tg T细胞和B细胞的培养物中，可诱导IgA的分泌。利用肠道免疫系统细胞检测食物成分的免疫功能，(1)研究了膳食核苷酸对肠道相关淋巴组织反应的影响。添加核苷酸（NT（+）饲粮）的BALB/c小鼠的t细胞受体(TCR) γ - 0上皮内淋巴细胞（IEL）比例显著高于不添加核苷酸的对照组。与对照组相比，NT（+）喂养小鼠的肠上皮细胞（IEC）产生了更高水平的互锁（IL-） 7和TGF-β，它们分别在TORγδo^+ IEL和IgA反应中起重要作用。将核苷酸添加到小鼠IEC原代培养物中，EL-7的分泌增加，而TGF-β的分泌没有增加。这些结果表明，核苷酸可以直接改变IEC中IL-7的分泌；提示NT（+）饮食增加小鼠IEC中IL-7分泌的机制与TGF-β分泌增加的机制不同。(2)口服用于食品容器的增塑剂柠檬酸乙酰三丁酯（ATBC）可影响ova喂养的TCR-Tg小鼠肠道组胺含量，提示ATBC可改变肠道内的过敏反应。

项目成果

H.Hamada, et al.: "Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine"J. Immunol.. 168. 57-64 (2002)

H.Hamada 等人：“小鼠小肠肠肠壁上多个分离的淋巴滤泡的鉴定”J.

K. Asai, et al: "Orally tolerant CD4 T cells respond poorly to antigenic stimulation but strongly direct stimulation of intracellular signaling pathways"Cytotechnology. 36. 145-153 (2001)

K. Asai 等人：“口服耐受的 CD4 T 细胞对抗原刺激反应较差，但对细胞内信号传导途径有强烈的直接刺激”。

S.Nagafuchi, et.al.: "Dietary nucleotides can up-regulate antigen-specfic Th1 immune responses and suppress antigen-specific IgE responses in mice."Int.Arch.Allergy Immunol.. 122. 33-41 (2000)

S.Nagafuchi 等人：“膳食核苷酸可以上调小鼠中抗原特异性 Th1 免疫反应并抑制抗原特异性 IgE 反应。”Int.Arch.Allergy Immunol.. 122. 33-41 (2000)

K.Suzuki, et.al.: "Gut Cryptopatches : direct evidence of extrathymic anatomical sites for intestinal T lymphopoiesis."Immunity. 13. 691-702 (2000)

K.Suzuki 等人：“肠道隐斑：肠道 T 淋巴细胞生成的胸腺外解剖部位的直接证据。”免疫。

Y.Ueda, et.al.: "Apoptosis of antigen-specific T cell induced by oral administration of antigen : comparison of intestinal and non-intestinal immune organs."Biosci.Biotechnol.Biochem.. (in press).

Y.Ueda 等人：“口服抗原诱导的抗原特异性 T 细胞凋亡：肠道和非肠道免疫器官的比较。”Biosci.Biotechnol.Biochem..（出版中）。