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.

肥胖相关的炎症最近因其毁灭性的19个炎症而接受，肥胖症中的年代炎症水平较低。脂肪组织稳态会导致抗压和肥胖的炎症反应的变化与野生型小鼠相比，与γδT-细胞 - 细胞 - 细胞funtose funtose组织的稳态相比，体重上的小鼠在jaml蛋白timulat或组织的γδT细胞中显着通过查看发育期间肥胖期间γδT细胞的脂肪细胞差异分化和稳态的直接来研究这些小鼠的发育肥胖机制。