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The Role of the Adrb3/IL6 Axis in the Impact of Psychosocial Stress on Lupus Pathogenesis

Adrb3/IL6 轴在心理社会压力对狼疮发病机制影响中的作用

基本信息

批准号：
10557799
负责人：
Andrew Wang
金额：
$ 44.46万
依托单位：
YALE UNIVERSITY
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：
2022-02-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10557799
关键词：
Acute Adipocytes Adrenal Glands Adverse effects Agonist Animal Housing Animals Antibodies Antibody Response Autoantibodies Autoimmune Diseases Autoimmunity B-Lymphocytes Biological Biological Assay Body Temperature Brain Catecholamines Cells Chronic Chronic stress Confusion Data Development Disease Disease Outcome Event Flare Genetic Glucocorticoids Glucose Goals Helper-Inducer T-Lymphocyte Hepatic Hepatocyte House mice Housing Human IL6 gene Immune Immunity Inflammatory Response Laboratory mice Life Stress Link Lupus Mediating Metabolic Methods Modeling Mus Myeloid Cell Activation Operative Surgical Procedures Outcome Pathogenesis Pathway interactions Patients Physiologic Thermoregulation Play Production Proteinuria Psychosocial Stress Receptors, Adrenergic, beta-3 Renal function Reporting Role Signal Transduction Source Stress Systemic Lupus Erythematosus Temperature Testing Thermogenesis Translations acute stress antagonist comparison control environmental enrichment for laboratory animals fighting genetic approach glucose metabolism hepatic gluconeogenesis immune activation improved insight mortality mouse model neurotransmission novel perceived stress pharmacologic plasma cell differentiation pre-clinical prototype psychosocial psychosocial stressors renal damage response rheumatologist

项目摘要

PROJECT SUMMARY Psychosocial stress has been well-documented to correlate with systemic lupus erythematosus (SLE) flares and poor SLE outcomes. How this occurs has not been well studied. We recently identified that psychosocial stress induces circulating IL6 produced by Adrb3-expressing brown adipocytes. Brown adipocyte-derived IL6 mediates immunometabolic reprogramming through hepatic IL6 signaling to support “fight or flight” responses to acute stress. We have generated preliminary data that chronic psychosocial stress may enhance mortality in murine models of SLE through this novel Adrb3/IL6 pathway. Here, we propose to dissect the role of the Adrb3/IL6 pathway in the impact of psychosocial stress on SLE pathogenesis in murine models. In addition to gaining biological insight into how psychosocial stress leads to increased immune activation in lupus, our studies would provide compelling pre-clinical data for potential human translation.

项目总结心理社会压力与系统性红斑狼疮(SLE)症状有很好的相关性。和不良的系统性红斑狼疮预后。这是如何发生的，还没有得到很好的研究。我们最近发现了心理社交应激诱导表达ADRB3的棕色脂肪细胞产生循环IL-6。棕色脂肪细胞来源的白介素6 通过肝脏IL6信号调节免疫代谢重编程以支持“战或逃”反应严重的压力。我们已经产生了初步数据，慢性心理社会压力可能会增加通过这种新的ADRB3/IL6途径建立小鼠系统性红斑狼疮模型。在这里，我们建议剖析 ADRB3/IL6通路在心理社会应激对小鼠系统性红斑狼疮发病机制中的影响除了……之外获得关于心理社会压力如何导致狼疮免疫活性增强的生物学见解，我们的研究将为潜在的人类翻译提供令人信服的临床前数据。