JAML-CAR regulation of adipose tissue homeostasis

JAML-CAR对脂肪组织稳态的调节

基本信息

批准号：
10217488
负责人：
Dianne B Mckay
金额：
$ 26.63万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
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：
2021-02-09 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10217488
关键词：
Address Adipocytes Adipose tissue Age Anti-Inflammatory Agents Antigens Attention Automobile Driving Body Weight CD3 Antigens COVID-19 Cardiovascular Diseases Cardiovascular system Cell Differentiation process Cell physiology Cells Chronic Classification Clinical Trials Data Development Disease Eating Economic Burden Epidemic Event Fasting Fatty Acids Genes Glucose Health Homeostasis Human Immune Immune response Immune system Immunity Immunologic Surveillance Impairment Inflammation Inflammatory Inflammatory Response Insulin Insulin Resistance Interleukin-17 Lead Ligands Link Lipids Lymphoid Cell Lymphoid Tissue Mediating Metabolic Metabolism Mucous Membrane Mus Nomenclature Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Obesity associated disease Pathway interactions Patients Play Population Prevention Production Proteins Regulation Regulatory T-Lymphocyte Reporting Research Role Site Source Stress Stromal Cells T-Lymphocyte TNF gene Temperature Testing Thermogenesis Time Tissues Update Wild Type Mouse ZNF145 gene adipocyte differentiation assault blood glucose regulation cell type cytokine environmental change glucose uptake improved insulin sensitivity lipid biosynthesis new therapeutic target novel therapeutic intervention obesity development obesity prevention obesity treatment pathogen receptor response systemic inflammatory response targeted treatment transcriptome sequencing uptake γδ T cells

项目摘要

Obesity and obesity-related diseases are at epidemic levels globally (WHO). Obesity-associated inflammation has recently received much attention due to its devastating consequences for many patients suffering from COVID-19. The low levels of chronic inflammation in obesity have led to the updated classification of obesity as an inflammatory disease that results from disturbed metabolic homeostasis. Crosstalk among immune cells and metabolic regulatory cells, such as adipocytes, in the adipose tissue regulate adipose tissue homeostasis. Cell intrinsic and environmental changes can lead to stress and alterations in cytokine production driving an inflammatory response that builds to metabolic decline and development of obesity. Adipose tissue contains populations of tissue-resident immune cells including γδ T cells that produce significant amounts of IL-17A and TNF-α when activated. IL-17 plays roles in regulation of body weight, adipocyte differentiation and insulin and glucose homeostasis. Mice deficient in the JAML protein that is costimulatory for tissue-resident γδ T cells become significantly obese with age compared to wildtype mice with similar food intake. We hypothesize that JAML-CAR interactions play a critical role in regulation of γδ T cell functions to maintain adipose tissue homeostasis. We plan to investigate the mechanism for development of obesity in these mice by looking at direct control of adipocyte differentiation and homeostasis by γδ T cells during development of obesity.

肥胖和与肥胖相关的疾病在全球流行病（WHO）。肥胖相关的炎症最近由于对许多Covid-19患者的毁灭性后果而受到了很多关注。肥胖症中慢性炎症的水平较低，导致肥胖症的最新分类为炎症性疾病，这是由于代谢性稳态受到干扰而导致的。脂肪组织中的免疫细胞和代谢调节细胞（例如脂肪细胞）之间的串扰调节脂肪组织稳态。细胞内在和环境变化会导致细胞因子产生的压力和改变，促进炎症反应，从而促进代谢下降和肥胖的发展。脂肪组织包含组织居住的免疫细胞种群，包括γδT细胞，这些细胞在激活时产生大量IL-17A和TNF-α。 IL-17在JAML蛋白的确定性小鼠中扮演角色，与具有相似食物摄入的野生型小鼠相比，组织居住的γδT细胞随着年龄的增长而变得显着肥胖。我们假设JAML卡车相互作用在调节γδT细胞功能以维持脂肪组织稳态方面起关键作用。我们计划通过查看肥胖发育过程中γδT细胞对脂肪细胞分化和稳态的直接控制来研究这些小鼠肥胖的发展机制。