Role of Natural Killer Cells in Myocarditis and Dilated Cardiomyopathy

自然杀伤细胞在心肌炎和扩张型心肌病中的作用

• 批准号: 8544199
• 负责人: SuFey Ong
• 金额: $ 4.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-03 至 2014-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8544199
• 关键词: Activated Natural Killer Cell; Affect; Age; Animals; Antigen-Presenting Cells; Autoimmune Diseases; Autoimmune Process; Biological Response Modifier Therapy; CD4 Positive T Lymphocytes; Cardiac; Cardiac Myocytes; Cell Differentiation process; Cell Lineage; Cells; Cessation of life; Chemotaxis; Coculture Techniques; Data; Depressed mood; Development; Dilated Cardiomyopathy; Disease; Environment; Eotaxin; Etiology; Fibroblasts; Fibrosis; Heart; Heart Transplantation; Heart failure; Helper-Inducer T-Lymphocyte; Immune; Immune system; In Vitro; Individual; Infiltration; Inflammation; Inflammatory; Interleukin-17; Interleukin-5; Laboratories; Life; Measures; Messenger RNA; Modeling; Mus; Myocarditis; Myocardium; Natural Killer Cells; Pathology; Patients; Peptides; Population; Process; Production; Reporting; Research; Role; Severity of illness; Staging; Sudden Death; T cell response; T-Cell Activation; T-Cell Development; T-Lymphocyte; T-Lymphocyte Subsets; Transgenic Mice; cytokine; effective therapy; eosinophil; granulocyte; high risk; human CCL26 protein; in vivo; member; migration; novel; sudden cardiac death; trafficking; young adult

DESCRIPTION (provided by applicant): Myocarditis, the inflammation of the heart muscle, is a one of the leading causes of cardiac-related deaths in individuals under the age of 40. Clinically, more than a third of myocarditis cases proceed irreversibly into dilated cardiomyopathy (DCM) which requires cardiac transplantation. Depletion of natural killer (NK) cells during of experimental autoimmune myocarditis (EAM) significantly increases levels of disease severity, providing evidence that NK cells can protect against inflammation. This increase was accompanied by expansions in Th2 and Th17 T cell subsets. Additionally, increases of eosinophils in the heart were also observed. This suggests that NK cells can directly interact with both members of the adaptive immune system and granulocytes. This proposal seeks to elucidate the mechanisms by which NKs modulate T cell responses in vivo and in vitro by depleting NK cells during different disease timepoints and by co-culturing NK cells with na¿ve T cells under polarizing conditions. This proposal also aims to understand the relationship between NK cells and eosinophils by determine the role of NK cells in regulating eosinophil chemotaxis. All together, this research will provide a strong background for a novel and much needed biological therapy for myocarditis.

描述（由申请人提供）：心肌炎（心肌炎症）是 40 岁以下个体心脏相关死亡的主要原因之一。临床上，超过三分之一的心肌炎病例不可逆地发展为扩张型心肌病实验性自身免疫性心肌炎 (EAM) 期间需要心脏移植的自然杀伤 (NK) 细胞 (DCM) 会显着增加疾病的严重程度，这提供了 NK 细胞可以减少疾病严重程度的证据。此外，还观察到心脏中嗜酸性粒细胞的增加，这表明 NK 细胞可以直接与适应性免疫系统的成员和粒细胞相互作用。旨在阐明 NK 在体内和体外通过在不同疾病时间点消耗 NK 细胞以及通过与 na 共培养 NK 细胞来调节 T 细胞反应的机制。该提案还旨在通过确定 NK 细胞在调节嗜酸性粒细胞趋化性中的作用来了解 NK 细胞和嗜酸性粒细胞之间的关系。总之，这项研究将为一种新颖且急需的生物疗法提供强有力的背景。用于心肌炎。