Leptin-based intervention in systemic autoimmunity

基于瘦素的系统性自身免疫干预

• 批准号: 7038254
• 负责人: ANTONIO LA CAVA
• 金额: $ 22.63万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7038254
• 关键词: autoimmunity; biological signal transduction; cellular pathology; disease /disorder model; enzyme linked immunosorbent assay; female; helper T lymphocyte; hormone inhibitor; hormone regulation /control mechanism; immunopharmacology; immunotherapy; laboratory mouse; leptin; longitudinal animal study; molecular pathology; nonhuman therapy evaluation; pathologic process; recombinant proteins; serology /serodiagnosis; systemic lupus erythematosus

DESCRIPTION (provided by applicant): Leptin is a hormone primarily involved in the regulation of basal metabolism that also has an important role in immune responses. Leptin promotes inflammation and can accelerate onset and progression of several autoimmune diseases including systemic lupus erythematosus (SLE). Because of that, we will test whether leptin-based intervention may be beneficial for the course of SLE in a mouse model of SLE, the (NZB x NZW)F1 (NZB/W F1) mouse. Since we hypothesize that leptin affects the phenotype and function of some immune-cell subsets and intereferes/promotes the release of soluble mediators in order to exert its propathogenic effects in SLE, we will dissect several cellular and molecular events induced by leptin in NZB/W F1 mice. We will study the effects of leptin on autoreactive T cells and will characterize some intracellular signaling events induced by leptin. We will then test different approaches of leptin-based intervention in these mice to ultimately set the stage for translational studies to humans. By defining some crucial aspects related to the physiopathology of leptin in the development of systemic autoimmunity in NZB/W F1 mice, these studies will explore new strategies of therapeutic intervention in lupus mice for future translational research in humans aimed at improving management of this incurable disease.

描述（由申请人提供）：瘦素是一种主要参与基础代谢调节的激素，在免疫应答中也具有重要作用。瘦素可促进炎症，并可加速包括系统性红斑狼疮（SLE）在内的几种自身免疫性疾病的发作和进展。因此，我们将在SLE小鼠模型（NZB x NZW）F1（NZB/W F1）小鼠中测试基于瘦素的干预是否有益于SLE的病程。由于我们假设瘦素影响某些免疫细胞亚群的表型和功能，并干扰/促进可溶性介质的释放，以发挥其在SLE中的致病作用，我们将解剖瘦素在NZB/WF 1小鼠中诱导的几个细胞和分子事件。我们将研究瘦素对自身反应性T细胞的影响，并描述瘦素诱导的一些细胞内信号传导事件。然后，我们将在这些小鼠中测试基于瘦素的干预的不同方法，以最终为人类的转化研究奠定基础。通过定义与瘦素在NZB/W F1小鼠全身性自身免疫发展中的生理病理学相关的一些关键方面，这些研究将探索狼疮小鼠治疗干预的新策略，用于未来人类的翻译研究，旨在改善这种不治之症的管理。

项目成果

Natural and adaptive immune cell-based therapies in autoimmunity.

自身免疫中基于自然和适应性免疫细胞的疗法。

• DOI: 10.2174/092986706777442020
• 发表时间: 2006
• 期刊: Current medicinal chemistry
• 影响因子: 4.1
• 作者: LaCava,Antonio;Shi,Fu-Dong
• 通讯作者: Shi,Fu-Dong

Autoimmunity and celiac disease.

自身免疫和乳糜泻。

• DOI: 10.2174/138955708783498113
• 发表时间: 2008
• 期刊: Mini reviews in medicinal chemistry
• 作者: Gianfrani,Carmen;Troncone,Riccardo;LaCava,Antonio
• 通讯作者: LaCava,Antonio