INDUCTION AND REGULATION OF IMMUNE AND ALLERGIC RESPONSES BY FOOD-DERIVED IMMUNE FUNCTIONAL MOLECULES

食物来源的免疫功能分子对免疫和过敏反应的诱导和调节

• 批准号: 13306010
• 负责人: KAMINOGAWA Shuichi
• 金额: $ 30.2万
• 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 (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13306010/
• 关键词: food allergy; intestinal immune system; T cell; intraepithelial lymphocytes(IEL); oral tolerance; IgE; intestinal epithelial cells; raffinose; DNAマイクロアレー; プロテオーム解析; 小腸上皮細胞(IEC)

1. Molecular biological analysis of characteristics of gut immunity (1) DNA microarray analysis identified genes expressed more abundantly in IEL than in spleen T cells. (2) We also elucidated the change in the gene expression pattern in EEL when ovalbumin (OVA)-specific T-cell receptor transgenic (TCR-Tg) mice were fed an egg-white diet. (3) The method for the primary culture of murine fetal intestinal epithelial cells was established and its capability for antigen presentation was shown.2. Analysis of mechanisms of oral tolerance induction (1) We showed that oral tolerance was induced in PP-deficient mice. (2) Intracellular proteins specifically expressed in orally tolerized CD4 T cells were determined by two-dimensional electrophoresis and mass spectrometric analysis. The results demonstrated that Caspase 3 was upregulated in orally tolerant CD4 T cells. (3) Genes expressed specifically in orally tolerized CD4 T cells were cloned using subtractive hybridization.3. Analysis of food allergy model, and suppression of food allergic reactions by food-derived immune functional molecules. (1) Feeding OVA diet to OVA-specific TCR-Tg mice resulted not only in induction of a serum IgE response, but also in inflammation in the small intestine. OVA-specific antibodies elicited by feeding OVA recognized mainly the tertiary structure of OVA. (2) OVA-specific IgE production and the decrease in body weight induced in this food-allergy model were shown to be suppressed by administering a TCR-antagonistic analog of the antigenic OVA peptide. (3) Feeding raffinose, which is known to modulate intestinal microflora, suppressed the IgE response in this food allergy model. (4) We also showed that the cytokine secretion pattern of naive CD4+ T cells were altered depending on the dose of OVA-derived peptide as an antigenic peptide.

1.肠道免疫特性的分子生物学分析(1)DNA微阵列分析显示IEL细胞表达的基因比脾T细胞表达的基因更丰富。(2)我们还阐明了卵清蛋白(OVA)特异性T细胞受体转基因(TCR-TG)小鼠饲喂蛋清后鳗鱼基因表达模式的变化。(3)建立了小鼠胎肠上皮细胞的原代培养方法，并对其抗原提呈能力进行了研究。口服耐受诱导机制的分析(1)我们发现PP缺陷小鼠可诱导口服耐受。(2)双向凝胶电泳法和质谱仪检测口服耐受的CD4T细胞内特异表达的蛋白质。结果表明，Caspase3在口服耐受的CD4T细胞中表达上调。(3)利用消减杂交技术克隆了口服耐受的CD4T细胞中特异表达的基因。食物过敏模型分析，以及食物来源免疫功能分子对食物过敏反应的抑制。(1)给OVA特异性TCR-TG小鼠饲喂OVA饲料，不仅能诱导血清IgE反应，还能引起小肠炎症反应。饲喂卵清蛋白所产生的卵子特异性抗体主要识别卵清蛋白的三级结构。(2)给予抗原性OVA多肽的TCR拮抗剂类似物可抑制该食物过敏模型中OVA特异性IgE的产生和体重下降。(3)在该食物过敏模型中，喂食棉子糖可抑制肠道菌群，抑制IgE反应。(4)我们还发现，初始的CD4+T细胞的细胞因子分泌模式随OVA衍生肽作为抗原肽的剂量而改变。

项目成果

Dendritic cells from spleen, mesenteric lymph node and Peyer's patch can induce both production of IL-4 and IFN-γ of naive CD4^+ T cells in their primary culture, depending on antigen doses.

来自脾脏、肠系膜淋巴结和派尔氏集结的树突状细胞可以诱导原代培养物中幼稚 CD4^+ T 细胞产生 IL-4 和 IFN-γ，具体取决于抗原剂量。

• 发表时间: 2003
• 期刊: Cytotechnology 43
• 作者: Masanobu Hibi;Satoshi Hachimura;Wataru Ise;Ayuko Sato;Tadashi Yoshida;Tsuyoshi Takayama;Kastumi Sasaki;Takashi Senga;Shuichi Hashizume;Mamoru Totsuka;Shuichi Kaminogawa.
• 通讯作者: Shuichi Kaminogawa.

Splenic dendritic cells from antigen-fed mice induced antigen-specific T cell unresponsiveness in vrvo.

来自饲喂抗原的小鼠的脾树突状细胞在体外诱导抗原特异性 T 细胞无反应。

• 期刊: Cytotechnology (in press)
• 作者: M.Hibi;et al.
• 通讯作者: et al.

M.Hibi, et al.: "Dendritic cells from spleen, mesenteric lymph node and Peyer's patch can induce both production of IL-4 and IFN-γ of naive CD4^+ T cells in their primary culture, depernding on antigen doses"Cytotechnology. (in press).

M.Hibi 等人：“来自脾脏、肠系膜淋巴结和派尔氏集结的树突状细胞可以诱导原代培养物中幼稚 CD4^+ T 细胞产生 IL-4 和 IFN-γ，具体取决于抗原剂量” （在新闻）。

H.Kano, et al.: "Oral intake of Lactobacillus delbruechii subsp. bulgaricus OLL1073R-1 prevents arthritis in mice"J. Food Prot.. 65. 153-160 (2002)

H.Kano 等人：“口服德氏乳杆菌保加利亚亚种 OLL1073R-1 可预防小鼠关节炎”

バイエル板樹状細胞の特性

拜尔斑树突状细胞的特征

• 发表时间: 2002
• 期刊: 臨床免疫 37
• 作者: 佐藤あゆ子;ら
• 通讯作者: ら