Characterization of CD8a cells as a novel immune population of the intestines

CD8a 细胞作为肠道新型免疫群体的表征

• 批准号: 9252837
• 负责人: Danyvid Olivares-Villagomez
• 金额: $ 15.83万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9252837
• 关键词: Acute; Antibodies; Biological; Biological Process; Biology; Cell physiology; Cells; Colitis; Development; Disease; Epithelial; Epithelium; Foundations; Gene Expression Profile; Goals; Health; Homeostasis; Human; Immune; Immune system; Inflammation; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestinal Mucosa; Intestines; Laboratories; Location; Lymphocyte; Lymphoid; Lymphoid Cell; Maintenance; Modeling; Molecular; Molecular Profiling; Mucosal Immune Responses; Mucosal Immunity; Mus; Myelogenous; Phenotype; Population; Process; Production; Research Proposals; Role; Surface; T-Cell Receptor; TNFRSF5 gene; Technology; chemokine; cytokine; human study; human subject; human tissue; insight; intestinal epithelium; intraepithelial; microorganism; mouse model; next generation sequencing; novel; response; tissue regeneration; transcription factor; transcriptome sequencing

 DESCRIPTION (provided by applicant): In this application we propose to investigate the biological features of a novel lymphoid population present in the intestinal epithelium. A hallmark of this population is the expression of CD8a and the production of cytokine/chemokine that indicate an innate immune phenotype. Therefore, we refer to this population as innate CD8a+ (iCD8a+) cells. Because of these features and their anatomical location within the intestinal epithelium, we hypothesize that iCD8a+ cells are a novel innate lymphoid population with an important biological function in mucosal immune responses of the intestine. In this proposal we will explore the biological role of iCD8a+ cells by primarily focusing on the phenotypic and molecular characterization of these cells, and their potential role in mucosal immune responses. For these purposes we propose the following complementary, yet independent aims: Aim 1. To assess the contribution of epithelial iCD8a+ cells in mucosal immunity. We will study the role on iCD8a+ cells in an acute model of intestinal inflammation induced by administration of anti-CD40 antibodies, with special emphasis on how these cells collaborate and/or influence other immune populations present in the intestinal mucosa, and the impact of these interactions during inflammation and colitis development. Aim 2. To characterize the lineage development and molecular expression profile of iCD8a+ cells. We will study the gene expression profile of iCD8a+ cells by using state-of-the-art next generation sequencing (RNA-seq) technology. The information obtained from this analysis will help us understand the lineage development of iCD8a+ cells and will further provide an indication of their putative role in mucosal immune responses. Successful completion of this project will provide important foundation for the understanding of the biology of iCD8a+ cells which will allow in depth characterization of this population in human tissue, and determine the impact of iCD8a+ cells on health and disease.

 描述（由申请人提供）：在本申请中，我们建议研究肠上皮中存在的新型淋巴群体的生物学特征。一个标志 该群体的特征是 CD8a 的表达和细胞因子/趋化因子的产生，表明先天免疫表型。因此，我们将该群体称为先天 CD8a+ (iCD8a+) 细胞。由于这些特征及其在肠上皮内的解剖位置，我们假设 iCD8a+ 细胞是一种新型先天淋巴群体，在肠道粘膜免疫反应中具有重要的生物学功能。在本提案中，我们将通过主要关注这些细胞的表型和分子特征及其在粘膜免疫反应中的潜在作用来探索 iCD8a+ 细胞的生物学作用。为此，我们提出以下补充但独立的目标： 目标 1. 评估上皮 iCD8a+ 细胞在粘膜免疫中的贡献。我们将研究 iCD8a+ 细胞在施用抗 CD40 抗体诱导的急性肠道炎症模型中的作用，特别强调这些细胞如何协作和/或影响肠粘膜中存在的其他免疫群体，以及这些相互作用在炎症和结肠炎发展过程中的影响。目标 2. 表征 iCD8a+ 细胞的谱系发育和分子表达谱。我们将利用最先进的下一代测序 (RNA-seq) 技术研究 iCD8a+ 细胞的基因表达谱。从该分析中获得的信息将帮助我们了解 iCD8a+ 细胞的谱系发育，并将进一步表明它们在粘膜免疫反应中的假定作用。该项目的成功完成将为了解 iCD8a+ 细胞的生物学提供重要基础，从而深入表征人体组织中的这一群体，并确定 iCD8a+ 细胞对健康和疾病的影响。