Role of RORgt+ (note: g: is gamma symbol) lymphocytes in Gut Tissue Homeostasis

RORgt（注：g：是伽玛符号）淋巴细胞在肠道组织稳态中的作用

基本信息

批准号：
10456906
负责人：
Liang Zhou
金额：
$ 56.05万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10456906
关键词：
Ablation Adoptive Transfer Affect Anabolism Anaerobic Bacteria Antibiotic Therapy Cell Compartmentation Cell Differentiation process Cell Maintenance Cell Proliferation Cell physiology Cells Cellular Metabolic Process Coculture Techniques DNA biosynthesis Data Development Disease Effector Cell Environment Epigenetic Process Epithelial Cells Exhibits Generations Genetic Genetic Transcription Glycolysis Helper-Inducer T-Lymphocyte Histologic Homeostasis Immune Immunity In Vitro Individual Infection Inflammation Inflammatory Bowel Diseases Interleukin-13 Interleukin-17 Interleukin-18 Length Lymphocyte Lymphocyte Biology Lymphocyte Function Lymphoid Cell Maintenance Mediating Metabolic Metabolism Metronidazole Mitochondria Mitochondrial DNA Modeling Molecular Molecular Mechanisms of Action Mus Mutant Strains Mice Orphan Oxidative Phosphorylation Paper Pathogenesis Phenotype Play Population Prevention Production Reactive Oxygen Species Regulation Respiration Retinoic Acid Receptor Role Small Intestines System T-Lymphocyte Tissues Tritrichomonas base cytokine enteric infection experimental study factor A gastrointestinal epithelium glucose metabolism gut microbiome helminth infection human disease immune function in vivo insight interleukin-22 intestinal homeostasis intestinal injury microbiome mitochondrial metabolism mtTF1 transcription factor novel novel therapeutics prevent programs receptor transcription factor transcriptome

项目摘要

Project Summary/Abstract: ILC3s, gdT17 and Th17 cells share common features, e.g., expressing the master transcription factor RORgt and the effector cytokines IL-17A, IL-17F and IL-22, and perform distinct immune functions under different environment context. Our preliminary data suggest that RORgt+ cell-intrinsic deletion of Tfam in Tfamfl/flRorc- cre mice affected RORgt+ gdT17 cells and ILC3s in vivo maintenance and led to small intestinal tissue remodeling via a tuft cell–ILC2 circuit. An emerging concept of mitochondrial control of immunity beyond ATP generation has recently been proposed. Based on the premise and our preliminary data, we hypothesize that that Tfam-mediated mitochondrial respiration in gdT17 cells and ILC3s is pivotal for gdT17/ILC3 cell homeostasis and regulation of small intestine tissue remodeling/metabolic changes and immunity/inflammation. Specifically, we will investigate 1) the role of Tfam in gdT17 and ILC3 lymphocyte maintenance, 2) the role of Tfam in gdT17 cells and/or ILC3s in regulating tuft cell-ILC2 circuit and small intestine tissue remodeling, and 3) the role of Tfam in gdT17 cells and/or ILC3s in regulation of microbiome and small intestinal immunity and inflammation. These experiments will offer an opportunity to elucidate Tfam- mediated mitochondrial respiration in RORgt+ lymphocytes in the small intestine under the steady state and during infection/immunity. Our study will provide novel cellular and molecular insights into the maintenance and function of gdT17 cells and ILC3s regulated by Tfam. Understanding the mechanisms underlying the requirement of Tfam for RORgt+ cells in regulation of small intestine tissue remodeling and immunity may represent a new paradigm for human disease treatment and/or prevention.

项目摘要/摘要： ILC3、gdT17 和 Th17 细胞具有共同特征，例如表达主转录因子 RORgt 以及效应细胞因子IL-17A、IL-17F和IL-22，在不同的条件下发挥不同的免疫功能。我们的初步数据表明，Tfamfl/flRorc- 中 RORgt+ 细胞固有地删除了 Tfam。 cre小鼠影响RORgt+ gdT17细胞和ILC3的体内维持并导致小肠组织通过簇细胞-ILC2 回路进行重塑是线粒体控制 ATP 之外免疫的新兴概念。基于这个前提和我们的初步数据，我们最近提出了这一点。 gdT17 细胞和 ILC3 中 Tfam 介导的线粒体呼吸对于 gdT17/ILC3 细胞至关重要小肠组织重塑/代谢变化的稳态和调节具体来说，我们将研究 1) Tfam 在 gdT17 和 ILC3 淋巴细胞中的作用。维护，2）gdT17细胞和/或ILC3中Tfam在调节簇细胞-ILC2电路和小细胞中的作用肠道组织重塑，以及 3) Tfam 在 gdT17 细胞和/或 ILC3 中调节微生物组和这些实验将为阐明 Tfam- 提供机会。稳定状态下小肠 RORgt+ 淋巴细胞介导的线粒体呼吸我们的研究将为感染/免疫期间的维持和免疫提供新的细胞和分子见解。 gdT17 细胞和 ILC3 受 Tfam 调节的功能。 Tfam 对 RORgt+ 细胞在调节小肠组织重塑和免疫方面的需求可能代表了人类疾病治疗和/或预防的新范例。