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。肠道免疫特征的分子生物学分析（1）DNA微阵列分析确定的基因在IEL中比在脾脏T细胞中更丰富。 （2）当卵形蛋白（OVA）特异性T细胞受体转基因（TCR-TG）小鼠被给卵白饮食喂食时，我们还阐明了EEL基因表达模式的变化。 （3）建立了鼠胎肠上皮细胞的原发性培养方法，并显示了其抗原表现的能力。2。分析口服耐受性诱导的机制（1）我们表明在缺乏PP的小鼠中诱导口服耐受性。 （2）通过二维电泳和质谱分析确定在口服耐受的CD4 T细胞中特异性表达的细胞内蛋白。结果表明，在口服耐受的CD4 T细胞中胱天蛋白酶3上调。 （3）使用减法杂交克隆在口服耐受的CD4 T细胞中特异性表达的基因3。食物过敏模型的分析以及食物来源的免疫功能分子抑制食物过敏反应。 （1）向OVA特异性TCR-TG小鼠喂食OVA饮食不仅引起了血清IgE反应，而且还导致小肠炎症。通过喂食OVA引起的OVA特异性抗体主要识别OVA的三级结构。 （2）通过给予抗原OVA肽的TCR抗抗酸类似物，证明了该食物过敏模型中oVA特异性的IgE产生和体重的减少。 （3）已知可以调节肠道微生物的灌注酸脂糖，在该食物过敏模型中抑制了IgE反应。 （4）我们还表明，幼稚CD4+ T细胞的细胞因子分泌模式根据OVA衍生的肽作为抗原肽的剂量而改变。

项目成果

Antigen presentation by Peyer's patch cells can induce both Th1- and Th2-type responses depending on antigen dosage, but a different cytokine response pattern from that of spleen cells.

派尔氏补片细胞的抗原呈递可诱导 Th1 型和 Th2 型反应，具体取决于抗原剂量，但细胞因子反应模式与脾细胞不同。

• 发表时间: 2002
• 期刊: Biosci. Biotechnol. Biochem 66
• 作者: T.Yoshida;et al.
• 通讯作者: et al.

プロバイオテックス、プレバイオテックスそして免疫

益生菌、益生元和免疫力

• 发表时间: 2002
• 期刊: 腸内細菌学雑誌 15
• 作者: Mukai;T.;Iida;K.;Sakaguchi;K.;Abe;K.;上野川修一
• 通讯作者: 上野川修一

K.Shida, et al.: "Lactobacillus casei strain Shirota suppresses serum IgE and IgG1 responses and systemic anaphylaxis in a food allergy model"Clin. Exp. Allergy. 32. 563-570 (2002)

K.Shida 等人：“干酪乳杆菌 Shirota 菌株在食物过敏模型中抑制血清 IgE 和 IgG1 反应以及全身过敏反应”Clin。

J.-Y.Kim, et al.: "In vitro immunopotentiating activity of cellular components of Lactococcus Lactis ssp. Lactis"J. Microbiol. Biotechnol.. (in press).

J.-Y.Kim 等人：“乳酸乳球菌乳球菌细胞成分的体外免疫增强活性”J.

A.Sato, et al.: "Murine Peyer's patch dendritic cells prime naive T cells to produce IFN-γ"Cytotechnology. (in press). (2002)

A.Sato 等人：“鼠派尔氏斑树突状细胞启动幼稚 T 细胞产生 IFN-γ”细胞技术（2002 年出版）。