Modulation of Autoantigen Trafficking and TLR engagement by FcgRIIB and AP3B1

描述(申请人提供)：我们的实验室致力于了解由DNA和/或RNA和抗体形成的致病免疫复合体(IC)如何在系统性红斑狼疮(SLE)的发病机制中做出贡献。我们使用体外和体内模型来确定DNA和/或RNA抗体复合体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交易如何影响功能结果。我们已经开发出同时也是pH传感器的新型集成电路。利用这些IC，我们可以快速筛选遗传因素和治疗药物对IC在B细胞和吞噬细胞中转运的影响。 公共卫生相关性：遗传、环境和自身免疫性疾病的发展之间的关系知之甚少。这项应用将试图了解在系统性红斑狼疮(SLE)患者中发现的真正的易感基因如何有助于自身免疫的发展。我们将通过在我们的SLE体外和体内模型中测试目前处于第二阶段临床试验的疗法来最大化对公共健康的影响。

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.