Microbiome and immunosenescence ofÂ T cells repertoire

T 细胞库的微生物组和免疫衰老

基本信息

批准号：
10661505
负责人：
LESZEK IGNATOWICZ
金额：
$ 39万
依托单位：
GEORGIA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10661505
关键词：
Age Aging Anti-Inflammatory Agents Antigens Bacteria CD4 Positive T Lymphocytes Cells Chronic Collection Data Disease Ecosystem Elderly Epitopes Equilibrium FOXP3 gene Functional disorder Genome Germ-Free Goals Grant Health Benefit Homeostasis Human Immune Immune system Immunity Immunization Individual Inflammation Interleukin-10 Intestines Longevity Mediating Metabolism Microbe Mucous Membrane Mus Patients Peptides Play Probiotics Regulatory T-Lymphocyte Rejuvenation Research Role Specificity Standardization System T-Lymphocyte TNFRSF11B gene Testing Therapeutic Transplantation Work age related commensal microbes cytokine design dysbiosis enteric pathogen gut inflammation gut microbiota immunoregulation immunosenescence improved intestinal homeostasis microbial microbiome microbiota microorganism antigen novel therapeutic intervention older patient pathogen exposure prevent response therapy design tissue injury transcription factor

项目摘要

The intestinal microbiota is a major contributor of antigens recognized by intestinal CD4 T cells. How these antigens influence CD4 T cells immunosenescence and their effector functions in old mice and humans remains unclear. Therefore, there is a need to develop a standardized microbial flora that has a manageable size and resembles natural microbiome that when administered to old, frail individuals will rebalance their intestinal homeostasis. The goal of this proposal is to test if this new oligoclonal collection of mouse intestinal commensals (oligo-MM), designed by system and genome-based approaches to recapitulate complete microbiome can help revitalize an aging immune system. In particular, we will investigate how oligo-MM microbiota and its main component Akkermasia municiphila interacts with Cd4 T cells and discover immune epitopes that these cells recognize from this bacteria. In Aim 1 we will investigate how specific intestinal commensals influence activation and repertoire of CD4 T cells in old mice. In our Aim 2 we will demonstrate that A. municiphila derived antigens induce naïve CD4Foxp3- T cells conversion to CD4Foxp3+ pTregs and substantially increase the number of these cells in old mice. We hypothesize that the therapeutic administration of A. municiphila to old mice can improve tolerance to intestinal microbiota and reduce immunosenescence. Overall this research will help develop new strategies based on strictly controlled microbiota-based therapies to control intestinal inflammation in elderly.

肠道菌群是肠CD4 t识别的抗原的主要因素细胞。在老鼠和人类中，尚不清楚。具有可管理尺寸并且类似于天然微生物组的微生物菌群由老年人管理的人将重新平衡肠道体内平衡。建议是测试这种小鼠肠道注释（Oligo -MM）的寡聚集合，由系统和基于基因组的方法设计用于回归全面微生物组的方法帮助振兴免疫系统。和主要成分Akkkermasia Municiphila与CD4 T细胞相互作用并发现免疫细胞从AIM 1中识别的表位。肠道的肠子在我们的目标2中影响CD4 T细胞的激活和曲目。我们将证明Aniciphila得出的抗原转化为CD4FOXP3+ PTREG，并大量增加了旧小鼠的这些细胞的数量。我们假设对肠道菌群的耐受性并减少免疫衰老。制定基于严格控制的基于微生物群的疗法以控制肠道的新策略老年人的炎症。