Investigation of immuno-regulatory competency of dietary substances and its application for our own beneficial ends

我们于2001年开始了上述研究项目，自2001年以来，肠道菌群、肠道上皮细胞(IEC)与局部和整体免疫反应之间的功能串扰已经积累了明显的特征。现在，很明显，肠道菌群和决定肠道菌群组成的饮食物质对于建立独特的肠道免疫反应特征是重要的。此外，推测现代饮食物质对肠道菌群的改变参与了溃疡性结肠炎和克罗恩病的发病机制。关于研究项目的总结，需要指出的是，我们澄清了肠道免疫反应的几个独特方面。首先，急性移植物抗宿主病(AGVHD)是由表达抗宿主特异性的免疫活性细胞毒性T细胞(CTL)引起的。我们首次证实，在一个特征良好的小鼠aGVHD模型中，肠道Peyer‘s Patches(PP)是激活抗宿主CTL反应所必需的。第二，我们证实了所有的淋巴结，包括肠系膜淋巴结、PP和分离的淋巴滤泡并不是新近发现的肠道隐斑(CP)的组织发生和无性系nu/nu小鼠发展γδ-IEL的绝对必要条件。这些结果表明，在淋巴系统极度耗竭的情况下，肠道CP可能是产生祖细胞γδ-IEL的解剖部位。第三，已证明依赖白介素15的传统树突状细胞和浆细胞样树突状细胞之间的串扰对于CpG诱导的免疫激活是必不可少的。综合所有这些新发现，我们积累了新的重要证据，这些证据对于研究饮食物质的免疫调节能力及其应用于我们自己的有益目的至关重要。

We started the above research project in 2001, and since 2001, distinctive features of functional crosstalk between intestinal flora, intestinal epithelial cells (IEC) and local as well as entire immune responses have been accumulated. Now, it is evident that intestinal flora and dietary substances that determine the composition of intestinal flora are important to the establishment of distinctive feature of intestinal immune response. Furthermore, it is speculated that the alteration of intestinal flora by modern dietary substances are involved in the pathogenesis of ulcerative colitis and Crohn's disease.With regard to the summary of the research project, it should be pointed out that we clarified several distinctive aspects of intestinal immune response. First, acute graft-versus-host disease (aGVHD) is initiated by immunologically competent cytotoxic T cells (CTL) that express anti-host specificities. We have corroborated for the first time that gut Peyer's patches (PP) are required to activate anti-host CTL response in a well characterized murine aGVHD model. Second, we have verified that all lymph nodes including mesenteric lymph nodes, PP and isolated lymphoid follicles are not an absolute requirement for the histogenesis of recently discovered gut cryptopatches (CP) and development of γδ-IEL in the athymic nu/nu mice. These results indicate that gut CP might be the anatomical sites to generate progenitor γδ-IEL under this extreme lymphoid depletion. Third, it has been demonstrated that interleukin 15-dependent crosstalk between conventional and plasmacytoid dendrite cells is essential for CpG-induced immune activation. Taking all of these new findings together, we have accumulated new important evidence that is essential for the investigation of immuno-regulatory competency of dietary substances and its application for our own beneficial ends.