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

我们从2001年开始了上述研究项目，自2001年以来，已经积累了肠道植物群、肠上皮细胞（IEC）和局部以及整体免疫应答之间的功能串扰的显著特征。现在，很明显，肠道植物群和决定肠道植物群组成的膳食物质对于建立肠道免疫应答的独特特征是重要的。此外，推测现代饮食物质对肠道植物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，应该指出的是，我们阐明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）由表达抗宿主特异性的免疫活性细胞毒性T细胞（CTL）引发。我们已经证实了第一次，需要肠道派尔集合淋巴结（PP）激活抗宿主CTL反应，在一个良好的特点，鼠aGVHD模型。第二，我们已经证实，所有淋巴结，包括肠系膜淋巴结，PP和孤立的淋巴滤泡不是最近发现的肠道cryptopatch（CP）的组织发生和无胸腺nu/nu小鼠中γδ-IEL发育的绝对要求。这些结果表明，肠道CP可能是在这种极端淋巴耗竭下产生祖细胞γδ-IEL的解剖学位点。第三，已经证明常规树突细胞和浆细胞样树突细胞之间的白介素15依赖性串扰对于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，这些证据对于研究膳食物质的免疫调节能力及其对我们自身有益的应用至关重要。

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.