Gene expression in Peyer's Patch FAE development

描述（由申请人提供）：Peyer's Patch滤泡相关上皮（FAE）提供粘膜淋巴组织的上皮屏障和抗原特异性递送到免疫系统。虽然FAE最著名的功能是M细胞介导的胞吞作用，但FAE的分化和功能必须作为一个整体来考虑。事实上，FAE应被视为一个复杂的组织，具有几个功能亚群，并与嵌入淋巴细胞和潜在免疫组织直接相互作用。我们已经确定了几个FAE相关基因，这些基因可能编码抗原胞吞作用到淋巴组织的特殊受体。其中一些受体也可能对粘膜免疫发出佐剂活性信号。我们的工作假设是FAE的功能是过滤分子进入Peyer's Patch，并作为先天免疫传感器。与这一观点一致的是，FAE细胞中某些基因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FAE亚群在体内发育生物学和功能方面的关系。提出了三个具体目标：FAE表型亚群是如何相关的？;具体目标2。在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细胞与固定前体或常见FAE肠细胞有区别吗？从这些研究中获得的信息将有助于了解肠道传染病的发病机制，并为设计粘膜疫苗提供重要的靶点。

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.