Immunometabolic Regulation of MDSCs in Periodontitis

牙周炎中 MDSC 的免疫代谢调节

基本信息

批准号：
10706535
负责人：
Keith L Kirkwood
金额：
$ 62.74万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
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：
2022-09-19 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10706535
关键词：
Adult Affect Alveolar Bone Loss Architecture Cardiovascular Diseases Cells Chronic Complex Diabetes Mellitus Diet Disease Disease Progression Disease susceptibility Enzymes Exposure to Flow Cytometry Functional disorder Funding Opportunities Future Genetic Gingiva Health Human Hyperglycemia Immune Immune system Immunophenotyping Incidence Inflammation Inflammation Mediators Label Leucocytic infiltrate Link Lipopolysaccharides Macrophage Memory Metabolic Metabolic Diseases Metabolism Molecular Mucosal Immunity Mus Myeloid Cells Myeloid-derived suppressor cells Nonesterified Fatty Acids Obesity Oral Oral cavity Osteoclasts Patients Periodontal Diseases Periodontal Infection Periodontitis Periodontium Phenotype Play Population Process Production Quality of life Regulation Risk Factors Role Severities Site Therapeutic Thinness Tissues Training adipokines alveolar bone alveolar destruction bone bone loss bone quality chronic inflammatory disease cohort comorbidity cytokine diet-induced obesity dietary gain of function immune function in vivo imaging insight loss of function microbial colonization monocyte obese patients obesity development osteoclastogenesis osteoimmunology peripheral blood recruit response systemic inflammatory response transcriptome sequencing transcriptomics

Adult Affect Alveolar Bone Loss Architecture Cardiovascular Diseases Cells Chronic Complex Diabetes Mellitus Diet Disease Disease Progression Disease susceptibility Enzymes Exposure to Flow Cytometry Functional disorder Funding Opportunities Future Genetic Gingiva Health Human Hyperglycemia Immune Immune system Immunophenotyping Incidence Inflammation Inflammation Mediators Label Leucocytic infiltrate Link Lipopolysaccharides Macrophage Memory Metabolic Metabolic Diseases Metabolism Molecular Mucosal Immunity Mus Myeloid Cells Myeloid-derived suppressor cells Nonesterified Fatty Acids Obesity Oral Oral cavity Osteoclasts Patients Periodontal Diseases Periodontal Infection Periodontitis Periodontium Phenotype Play Population Process Production Quality of life Regulation Risk Factors Role Severities Site Therapeutic Thinness Tissues Training adipokines alveolar bone alveolar destruction bone bone loss bone quality chronic inflammatory disease cohort comorbidity cytokine diet-induced obesity dietary gain of function immune function in vivo imaging insight loss of function microbial colonization monocyte obese patients obesity development osteoclastogenesis osteoimmunology peripheral blood recruit response systemic inflammatory response transcriptome sequencing transcriptomics

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项目摘要

PROJECT SUMMARY/ABSTRACT Periodontitis is a common chronic inflammatory disease affecting over half of the US adult population and characterized by destruction of the supporting structures of the teeth. Although there is a clear relationship between increased obesity and periodontal disease incidence, the mechanisms that underpin the links between these two conditions are not completely understood. Chronic low-grade systemic inflammation in response to obesity, referred to as metainflammation, is a consequence of immune dysregulation that results from the continuous exposure to bacterial lipopolysaccharide and saturated free fatty acids under hyperglycemic conditions. Obesity is known to cause the expansion of immature myeloid cells, termed myeloid-derived suppressor cell (MDSC) populations, which can differentiate into mature osteoclasts, resulting in alveolar bone loss. In this application, it is hypothesized that MDSC expansion and mobilization contribute towards obesity- associated periodontitis through MDSC metabolic reprograming with increased osteoclastic capacity contributing towards alveolar bone loss. The aims outlined in this application will address questions to determine: 1) the mechanisms that govern obesity-directed MDSC subpopulation mobilization and function in the periodontal microenvironment; 2) how obesity or HFD, independent of obesity, contributes toward M-MDSC osteoclastogenic reprogramming potential, and 3) if obesity status contributes towards differences in MDSC subpopulations in human periodontal disease. At the conclusion of these studies, new evidence will be provided related to the cellular mechanisms engaged during diet-induced obesity that contribute towards periodontal disease susceptibility and progression through MDSC populations in mice and humans.

项目摘要/摘要牙周炎是一种常见的慢性炎性疾病，影响美国成年人口一半以上，以破坏牙齿支撑结构的特征。虽然有明确的关系肥胖和牙周疾病发病率增加，支撑联系的机制这两个条件尚未完全理解。慢性低级全身炎症反应肥胖症，称为元炎症，是免疫失调的结果，是由在高血糖下连续暴露于细菌脂多糖和饱和游离脂肪酸状况。已知肥胖会导致未成熟的髓样细胞的膨胀，称为髓样衍生抑制细胞（MDSC）种群，可以区分成熟的破骨细胞，导致牙槽骨损失。在此应用中，假设MDSC的扩张和动员有助于肥胖通过MDSC代谢重编程相关的牙周炎，破骨碎屑能力增加面向牙槽骨质流失。本申请中概述的目的将解决问题以确定：1）控制肥胖指导的MDSC亚群动员和功能的机制微环境； 2）肥胖或HFD如何独立于肥胖，有助于M-MDSC破骨细胞构成重新编程潜力，3）如果肥胖状态有助于MDSC亚群的差异人牙周病。这些研究结束时，将提供与饮食引起的肥胖症中参与的细胞机制，有助于牙周疾病小鼠和人类中MDSC种群的敏感性和进展。