Chylomicron-responsive Tregs in EED

EED 中的乳糜微粒反应性 Tregs

基本信息

批准号：
10511826
负责人：
Timothy Wesley Hand
金额：
$ 23.82万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-08 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10511826
关键词：
Address Anti-Inflammatory Agents Antibiotics Biological Markers Blood Circulation Body Weight Bypass Calories Carbohydrates Characteristics Child Chronic Chylomicrons Clinical Cognitive Colon Coupled Diet Dietary Fats Dietary Intervention Disease Enteral Etiology Exhibits FOXP3 gene Fat-Restricted Diet Fatty acid glycerol esters Fistula Focus Groups Foundations Functional disorder Genus Hippocampus Goals Gold Growth Hand Human Inflammation Inflammatory Interleukin-10 Intestinal Absorption Intestinal Diseases Intestines Lipids Low Density Lipoprotein Receptor Lymph Malabsorption Syndromes Malnutrition Measures Medium chain triglycerides Mesentery Metabolic Metabolism Micronutrients Modeling Mus Nutritional Nutritional Support Pathology Pathway interactions Patients Pattern Pharmaceutical Preparations Plasma Politics Regulatory T-Lymphocyte Role Signal Transduction Small Intestines Source Testing Therapeutic Travel Triglycerides Tumor-infiltrating immune cells UNICEF Villus Weight absorption dietary drinking water dysbiosis experience global health in vivo lipid metabolism low income country microbiota mortality mouse model negative affect novel nutrient absorption reconstitution response restoration transcription factor transcriptome treatment strategy

项目摘要

Abstract. A quarter of the world’s children experience chronic malnutrition coupled with a lack of access to clean drinking water. This combination results in Environmental Enteric Dysfunction (EED), a disease where intestinal malabsorption exacerbates malnutrition, leading to increased cognitive deficiencies, stunted growth and mortality. The intestine of EED patients is characterized by inflammation and flattened villi in the small intestine that negatively affect absorptive capacity. Our groups have recently identified a pool of protective Tregs in the small intestine that respond specifically to dietary lipid absorption, to the presence or absence of chylomicrons secreted in response to dietary lipids, and to EED. We hypothesize that lipid absorption and chylomicron secretion is reduced in the EED intestine, that EED-chylomicrons deliver less dietary triglyceride to mesenteric LN Tregs, and that replenishing calories by bypassing the chylomicron pathway (with a medium-chain- triglycerides) will restore calories without blocking the effect EED-chylomicrons that will travel by the lymph to stimulate protective intestinal Tregs.

抽象的。世界四分之一的孩子经历了慢性营养不良，加上缺乏清洁饮酒的机会水。这种组合导致环境肠功能障碍（EED），一种肠道的疾病不良制剂加剧营养不良，导致认知缺陷增加，发育不良和死亡。 EED患者的肠道的特征是小肠炎症和扁平的绒毛这对吸收能力产生负面影响。我们的小组最近在小肠，专门针对饮食脂质滥用，cylonicrons的存在或不存在响应饮食脂质和EED分泌。我们假设脂质抽象和乳糜微粒在EED肠道中，分泌降低，EED - 纤维素较少的饮食甘油三酸酯对肠系膜甘油三酸酯较少 ln tregs，并通过绕过乳糜微粒途径来补充卡路里（用中链 - 甘油三酸酯）将恢复卡路里，而不会阻止淋巴传播的效果EED - 奇数刺激受保护的肠Treg。