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Regulation of Gut Innate Lymphoid Cells by Ahr

Ahr 对肠道先天淋巴细胞的调节

基本信息

批准号：
10734895
负责人：
Liang Zhou
金额：
$ 55.02万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10734895
关键词：
Ablation Affect Aryl Hydrocarbon Receptor Binding Cell Compartmentation Cell Line Cell Maintenance Cell physiology Cells Citrobacter rodentium Communicable Diseases Complex Data Development Disease Elements Environmental Impact Funding Genetic Transcription Glycolysis HIF1A gene Health Homeostasis IL17 gene Immune Immune response Immune system Immunity Immunology Infection Inflammation Intestinal Mucosa Intestines Iron Knowledge Lymphocyte Lymphoid Cell Maintenance Mediating Metabolic Metabolism Mitochondria Modeling Mus Oxidative Phosphorylation Pathway interactions Play Predisposition Production Proliferating Regulation Research Role Salmonella typhimurium T-Cell Activation TFRC gene Testing Tissues Transcriptional Regulation combat cytokine experimental study global health host microbiome in vivo insight interleukin-22 iron deficiency iron metabolism microbiome microbiota mouse genetics novel novel therapeutic intervention nutrition pathogen promoter receptor receptor expression tool transcription factor transcriptomics uptake

项目摘要

Project Summary/Abstract RORgt+ ILC3s are abundant in the intestinal mucosa and play critical roles in gut tissue homeostasis and host- microbiome interactions under the steady state, and also contribute to host immunity during infection and inflammation. As a fundamental element for normal development of the immune system, iron is important for the proliferation and activation of T cells, and participates in the complex interplays among host, commensals, and pathogens. Our preliminary data suggest that iron metabolism is important for ILC3 maintenance and function. Ahr together with other transcription factors regulate the transcription of CD71, a key iron transporter that is crucial for maintaining a functional ILC3 compartment in the gut. Based on the premise and our preliminary data, we hypothesize that iron metabolism regulated by the Ahr-CD71 axis is important for intestinal ILC3 maintenance and function. Specifically, we will investigate 1) the iron impact on ILC3 maintenance and function, 2) the regulation of CD71 expression by Ahr-mediated pathway in ILC3s, and 3) the functional role of Ahr-mediated CD71 pathway in ILC3s during infection. The study represents an emerging paradigm of immune metabolism and nutrition immunology in health and disease, Successful completion of proposed experiments will offer an opportunity to elucidate the Ahr-CD71 axis in ILC3s in the gut under the steady state and during infection, and shed new light on the profound effect of environmental impact on host immunity.

项目摘要/摘要 RORgT+ILC3s在肠粘膜中含量丰富，在肠道组织内稳态和宿主- 微生物群在稳定状态下的相互作用，并在感染和感染期间有助于宿主免疫发炎。作为免疫系统正常发育的基本元素，铁对 T细胞的增殖和激活，并参与宿主、共生体、和病原体。我们的初步数据表明，铁代谢对ILC3的维持和功能。AHR与其他转录因子一起调节关键的铁转运蛋白CD71的转录这对于维持肠道中ILC3的功能是至关重要的。基于这个前提和我们的初步数据，我们假设由AhR-CD71轴调节的铁代谢对肠道ILC3的维持和功能。具体地说，我们将调查1)铁对ILC3的影响维持和功能，2)通过AhR介导的途径调节CD71在ILC3中的表达，以及3) AhR介导的CD71通路在ILC3s感染过程中的作用这项研究代表了一种新兴的健康与疾病中的免疫新陈代谢和营养免疫学范式，圆满完成拟议的实验将为阐明肠道中ILC3的Ahr-CD71轴提供一个机会并揭示了环境影响对寄主的深刻影响豁免权。