Gene expression in Peyer's Patch FAE development

描述(申请人提供)：佩耶氏斑滤泡相关上皮(FAE)既提供黏膜淋巴组织的上皮屏障，也为免疫系统提供专门的抗原输送。虽然FAE最著名的功能是由M细胞介导的跨细胞作用，但必须将FAE的分化和功能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潜在的免疫组织直接相互作用。我们已经确定了几个FAE相关基因，它们可能编码特定的受体，使抗原跨细胞转运到潜在的淋巴组织。这些受体中的一些也可能发出粘膜免疫佐剂活性的信号。我们的工作假设是，FAE作为分子的过滤器进入Peyer‘s Patch，并作为先天免疫传感器。与这一概念一致，一些基因在FAE细胞中的表达似乎标志着不同的功能亚群。我们建议使用体外和体内模型对FAE进行研究，以揭示体内FAE亚群之间的发育生物学和功能的关系。提出了三个具体的目标：1.FAE表型亚群是如何相关的？2.在FAE和M细胞表型的分化过程中亚细胞重组是如何发生的？3.M细胞是否与承诺的前体细胞或普通的FAE肠细胞分化？所获得的信息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.