Elucidation of functional mechanisms of intestinal immune regulatory cells and recovery of immune function by foods using these cells as targets

阐明肠道免疫调节细胞的功能机制以及以这些细胞为靶点的食品恢复免疫功能

• 批准号: 17380076
• 负责人: HACHIMURA Satoshi
• 金额: $ 9.09万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17380076/
• 关键词: oral tolerance; allergv; intestinal immune system; IgA; regulatory T cell; functional food; dendritic cell; TLR; パイエル板; インターロイキン5; TLR

1. Analysis of intestinal cell populations that induce IgA production from B cells Intestinal IgA production is first line defense against infection. Therefore, cells that augment IgA production are targets for immuno-modulation by foods. We had identified Peyer's patch (PP) CD3-IL-2R^+ cells as a non-T non-B cell population producing high level of IL-5, and promoting IgA production in vitro. Expression of the microbial receptor TLRs in these cells, response of these cells to poly I:C (model ligand for virus RNA), and cell function in germ free mice were analyzed. The results suggested that CD3-IL-2R^+ cells recognize microbial components and virus infection and promote IgA production in the intestine. Further it was implied that CD3-IL-2R^+ cells are stimulated in PP and then migrate to the lamina propria. In addition, we examined the response of PP dendritic cells to TLR ligand stimuli, and obtained results which suggested that intestinal dendritic cells mediate B-cell independent IgA production against microbes through production of factors such as IL-6.2. Analysis of regulatory T cells in oral tolerance Oral tolerance is a suppressive mechanism for food allergy. Regulatory T cells in oral tolerance are good targets for immuno-modulation. CD62L^high/int CD44^intT cells and CD62L^lowCD44^highT cells were induced by oral administration of ovalbumin (OVA) in DO11.10 OVA-specific TCR transgenic mice. Both populations were anergic and possessed regulatory function. CD62L^low CD44^highT cells possessed stronger suppressive function, and induced apoptosis to co-cultured naive T cells effectively. Our results taken together demonstrate CD62L^high/int CD44^intT cells and CD62L^low CD44^highT cells are induced in oral tolerance, and each expressed different types of regulatory function.

1.分析从B细胞产生IgA的肠道细胞群分析肠道产生IgA是抵御感染的第一道防线。因此，增加IgA产生的细胞是食物免疫调节的目标。我们已经鉴定Peyer‘s Patch(PP)CD3-IL-2R^+细胞是一种非T非B细胞群，在体外产生高水平的IL-5，并促进IgA的产生。分析这些细胞中微生物受体TLRs的表达，这些细胞对Poly I：C(病毒RNA的模型配体)的反应，以及无菌小鼠的细胞功能。结果提示，CD3-IL-2R^+细胞识别微生物成分和病毒感染，促进肠道中IgA的产生。这进一步表明，在PP中CD3-IL-2R^+细胞被刺激，然后迁移到固有层。此外，我们还检测了PP树突状细胞对TLR配体刺激的反应，结果表明，肠道树突状细胞通过产生IL-6.2等因子来介导B细胞非依赖性IgA的产生。分析调节性T细胞在口服耐受中的作用口服耐受是食物过敏的一种抑制机制。口服耐受中的调节性T细胞是免疫调节的良好靶点。口服卵白蛋白(OVA)诱导DO11.10 OVA特异性TCR转基因小鼠CD62L/int CD44/intT细胞和CD62L/lowCD44/hight细胞。这两个种群都是无能的，都具有调节功能。CD62L、Low CD44、Hight细胞具有较强的抑制功能，可有效诱导共培养的初始T细胞发生凋亡。以上结果表明，口服耐受可诱导CD62L高/int CD44/intT细胞和CD62L/低CD44/intT细胞表达不同类型的调节功能。

项目成果

Oral antigen induces antigen-specific activation of intraepithelial CD4+ lymphocytes but suppresses their activation in spleen.

• DOI: 10.1016/j.imbio.2005.07.001
• 发表时间: 2005-11
• 期刊: Immunobiology
• 影响因子: 2.8
• 作者: H. Tamauchi;Y. Yoshida;Takehito Sato;S. Hachimura;M. Inoue;S. Kaminogawa;S. Habu

Lactobacillus acidophilus strain L-92 induces apoptosis of antigen-stimulated T cells

嗜酸乳杆菌菌株 L-92 诱导抗原刺激的 T 细胞凋亡

• 期刊: Immunobiology(掲載確定)
• 作者: H. Kanzato;et. al.
• 通讯作者: et. al.

Lactobacillus acidophilus L-92株による抗原刺激を受けたT細胞におけるアポトーシス誘導

嗜酸乳杆菌 L-92 菌株刺激 T 细胞凋亡的诱导

• 发表时间: 2005
• 作者: 勘里裕樹;他
• 通讯作者: 他

Dietary melibiose regulates Th cell response and enhances the induction of oral toleranc

膳食蜜二糖调节 Th 细胞反应并增强口服耐受的诱导

• 发表时间: 2007
• 期刊: Biosci. Biotechnol. Biochem 71
• 作者: K. Tomita;et. al.
• 通讯作者: et. al.

The role of Bifodiobacterium in the development of gut immune systems : analysis using gnotobiotic TCR-transgenic mice

双歧杆菌在肠道免疫系统发育中的作用：使用知生 TCR 转基因小鼠进行分析

• 发表时间: 2006
• 期刊: Animal Cell Technology : Basic & Applied Aspects 14
• 作者: M. Tsuda;et. al.
• 通讯作者: et. al.