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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.

项目总结/文摘: