Modulation of Autoantigen Trafficking and TLR engagement by FcgRIIB and AP3B1

FcgRIIB 和 AP3B1 对自身抗原运输和 TLR 参与的调节

• 批准号: 8397409
• 负责人: Krishna-sulayman Laroche Moody
• 金额: $ 2.96万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8397409
• 关键词: Actins; Adaptor Protein Complex 3; Affect; Antibodies; Antigen-Antibody Complex; Attention; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; B Cell Proliferation; B-Lymphocytes; Binding; Cells; Clinical; Complex; Confocal Microscopy; Cytoskeletal Modeling; DNA; Data; Defect; Dendritic Cells; Development; Disease; Effector Cell; Environment; Exhibits; Flow Cytometry; Genetic; Goals; Human; Immune; Immune Cell Activation; Immunoglobulin G; In Vitro; Interferon Type I; Interferons; Interleukin-6; Laboratories; Ligands; Lupus; Mediating; Modeling; Molecular; Monitor; Mus; Myelogenous; Nucleic Acids; Outcome; Pathogenesis; Patients; Pattern; Phagocytes; Phase II Clinical Trials; Phosphorylation; Process; Production; Proliferating; Public Health; RANTES; RNA; Resistance; Ribonucleases; Role; Signal Transduction; Susceptibility Gene; TLR7 gene; TNF gene; Testing; Therapeutic Agents; cytokine; functional outcomes; in vivo Model; inhibitor/antagonist; mouse model; novel; response; sensor; systemic autoimmune disease; trafficking

DESCRIPTION (provided by applicant): Our lab is focused on understanding how pathogenic immune complexes (IC) formed from DNA and/or RNA and antibodies contribute to the pathogenesis of systemic lupus erythematous (SLE). We use in vitro and in vivo models to determine the molecular mechanisms that govern the activation of immune cells by DNA and/or RNA antibody complexes. This particular project is investigating how IC trafficking within immune cells affects the functional outcome. We have developed novel ICs that are also pH sensors. Using these ICs we can rapidly screen the effect of genetic factors and therapeutic agents on IC trafficking in B cells and phagocytes. PUBLIC HEALTH RELEVANCE: The relationship between genetics, environment and the development of autoimmune disease is poorly understood. This application will try to understand how a bona fide susceptibility gene found in systemic lupus erythematous (SLE) patients contributes to the development of autoimmunity. We will maximize the public health impact by testing therapies that are currently in phase II clinical trials in our in vitro and in vvo models of SLE.

描述（由申请人提供）：我们的实验室专注于了解由DNA和/或RNA和抗体形成的致病性免疫复合物（IC）如何促进系统性红斑狼疮（SLE）的发病机制。我们使用体外和体内模型来确定DNA和/或RNA抗体复合物激活免疫细胞的分子机制。这个特别的项目正在研究免疫细胞内的IC运输如何影响功能结果。我们开发了新型的IC，也是pH传感器。利用这些IC，我们可以快速筛选遗传因素和治疗剂对IC在B细胞和吞噬细胞中运输的影响。 公共卫生相关性：人们对遗传、环境和自身免疫性疾病发展之间的关系知之甚少。本申请将试图了解如何在系统性红斑狼疮（SLE）患者中发现的真正的易感基因有助于自身免疫的发展。我们将通过在SLE的体外和体内模型中测试目前处于II期临床试验的疗法来最大限度地提高公众健康的影响。