Gene expression in Peyer's Patch FAE development

描述（由申请方提供）：派尔集合淋巴结滤泡相关上皮（FAE）提供粘膜淋巴组织上的上皮屏障和向免疫系统专门递送抗原。虽然FAE最著名的功能是M细胞介导的转胞吞作用，但FAE的分化和功能必须作为一个整体来考虑。事实上，FAE应该被视为一个复杂的组织，具有几个功能亚群，并与嵌入的淋巴细胞和免疫组织直接相互作用。我们已经确定了几个FAE相关基因，可能编码专门的受体转胞吞抗原的基础淋巴组织。这些受体中的一些也可能信号粘膜免疫的佐剂活性。我们的工作假设是，FAE的功能作为一个过滤器的分子获得进入派尔集合淋巴结，并作为一个先天性免疫传感器。与这一概念相一致，FAE细胞中某些基因的表达似乎标志着不同的功能子集。我们提出了一个研究FAE使用在体外和体内模型，以揭示FAE子集在体内的发育生物学和功能方面的关系。提出了三个具体目标：具体目标1。FAE表型亚群是如何相关的？;具体目标2。FAE和M细胞表型分化过程中亚细胞重组是如何发生的？具体目标3。M细胞是否从定向前体或普通FAE肠细胞分化而来？这些研究结果将有助于了解肠道传染病的发病机制，并为黏膜疫苗的设计提供重要的靶点。

DESCRIPTION (provided by applicant): The Peyer's Patch follicle associated epithelium (FAE) provides both an epithelial barrier over mucosal lymphoid tissue and specialized delivery of antigens to the immune system. Although the best-known function of the FAE is the transcytosis mediated by M cells, the differentiation and function of FAE must be considered as a whole. Indeed, the FAE should be viewed as a complex tissue, with several functional subsets, and direct interactions with embedded lymphocytes and underlying immune tissue. We have identified several FAE associated genes that may encode specialized receptors for transcytosis of antigens to underlying lymphoid tissue. Some of these receptors may also signal adjuvant activity for mucosal immunity. Our working hypothesis is that the FAE functions as a filter for molecules gaining access to the Peyer's Patch, and as an innate immune sensor. Consistent with this notion, expression of some genes among cells of the FAE appears to mark distinct functional subsets. We propose a study of FAE using both in vitro and in vivo models, to reveal the relationships among FAE subsets in vivo with respect to their developmental biology and function. Three specific aims are proposed: Specific aim 1. How are FAE phenotypic subsets related? ; Specific aim 2. How does sub-cellular reorganization occur during differentiation of FAE and M cell phenotypes? ; Specific aim 3. Do M cells differentiate from committed precursors or common FAE enterocytes? Information gained from the proposed studies will help the understanding of pathogenesis mechanisms of intestinal infectious diseases, and provide important targets in the design of mucosal vaccines.