Supplement: Immunometabolic and epigenetic effects of obesity on innate immune surveillance in cancer

补充：肥胖对癌症先天免疫监视的免疫代谢和表观遗传影响

• 批准号: 10211421
• 负责人: Lydia Lynch
• 金额: $ 44.75万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-28 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10211421
• 关键词: Affect; Age; Boston; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 pandemic; Cells; Cellular Metabolic Process; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic; Collaborations; Color; Communicable Diseases; Contracts; Coupled; Critical Care; Critical Illness; Dangerousness; Data; Defect; Diabetes Mellitus; Diagnosis; Disease; Disease Outbreaks; Elderly; Endocrine; Endocrinologist; Epigenetic Process; Flow Cytometry; Functional disorder; Future; Grant; Heart Abnormalities; Hospitals; Human; Immune; Immune response; Immune system; Immunologic Surveillance; Immunologics; Impairment; Individual; Infection; Inflammation; Influenza A Virus, H1N1 Subtype; Lead; Legal patent; Letters; Lung; Malignant Neoplasms; Measures; Medical center; Metabolic; Monitor; Morbidity - disease rate; Mus; Natural Killer Cells; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obesity associated disease; Parents; Pathogenesis; Pathology; Patients; Phenotype; Plasma; Play; Population; Positioning Attribute; Predisposing Factor; Predisposition; Production; Publishing; Reporting; Research; Research Personnel; Risk; Role; Sample Size; Sampling; Serum; Severe Acute Respiratory Syndrome; Severities; Severity of illness; Specialist; Symptoms; T cell response; T-Lymphocyte; Therapeutic; Thinness; Time; United States National Institutes of Health; Viral; Virus; Virus Diseases; Woman; base; biobank; checkpoint receptors; chemokine; cohort; cytokine; cytokine release syndrome; cytotoxicity; design; effective therapy; falls; innovation; metabolomics; mortality; mortality risk; novel; novel strategies; pandemic disease; parent grant; patient population; peripheral blood; prevent; response; seasonal influenza; synergism; therapeutic biomarker; therapeutic target; tumor

Project Summary The COVID-19 pandemic has affected millions worldwide, however it is clear that there are predisposing factors that lead to critical illness and mortality including older age, and underlying conditions particularly type 2 diabetes (T2DM) and obesity. The Centers for Disease Control and Prevention (CDC) has reported that patients with T2DM may have up to ten-times greater risk of death when they contract COVID-19. Understanding the immune response is critical to preventing or reducing mortality from COVID-19 and informing therapeutic strategies for this patient population. The overall aim of this proposal is to identify the immune basis for increased disease severity and death from COVID-19 in patients with obesity and T2DM. It is now appreciated that obesity is associated with immune dysregulation, which may be the cause of some obesity related diseases. For example, Natural killer (NK) cells, so-called due to their natural cytotoxicity against viruses and tumors, are unable to kill targets efficiently in obese humans and mice. We have recently found similar defects in CD8 T cells in patients with obesity and T2DM. The key unanswered questions are 1) are these immune defects responsible for the increased severity and death from COVID-19 in patients with obesity and T2DM 2) do patents with obesity and T2DM have an underactive or overactive (damaging cytokine storm) in response to COVID-19? and 3) is metabolic dysregulation at the heart of these defects? It is critical to understand the immune basis for this susceptibility in order to prevent or reduce mortality from COVID-19 and to inform therapeutic strategies in this patient populations. Findings from this study may lead to understanding the immune response in patients with obesity for future novel viral outbreaks.

项目摘要 COVID-19大流行已经影响了全球数以百万计的数百万，但是很明显 诱发重症疾病和死亡率（包括年龄较大）和基础的诱发因素 条件特别是2型糖尿病（T2DM）和肥胖症。疾病控制中心和 预防（CDC）报告说，T2DM患者的死亡风险可能更高 当他们签约Covid-19时。了解免疫反应对于预防或减少至关重要 COVID-19的死亡率，并为该患者人群提供治疗策略。总体 该提议的目的是确定疾病严重程度增加和死亡的免疫基础 肥胖症患者和T2DM患者的Covid-19。 现在感谢肥胖与免疫失调有关，这可能是 一些与肥胖有关的疾病。例如，自然杀手（NK）细胞，由于其自​​然而被所谓 针对病毒和肿瘤的细胞毒性无法在肥胖人和小鼠中有效杀死靶标。 我们最近发现肥胖症和T2DM患者的CD8 T细胞中的类似缺陷。钥匙 未解决的问题是1）这些免疫缺陷是否导致严重程度增加和 肥胖症患者和T2DM患者的死亡 - 肥胖症和T2DM的专利具有 响应于19的covid-19？ 3）是代谢 这些缺陷的核心失调？了解这一点至关重要 易感性，以防止或减少COVID-19的死亡率并为治疗策略提供信息 在这个患者人群中。这项研究的结果可能导致了解免疫反应 肥胖症患者未来新的病毒爆发。