Regulation of LAIR-1 in Lupus

描述（由申请人提供）：系统性红斑狼疮（SLE）是一种具有遗传和非遗传触发的自身免疫性疾病。已知C1q缺乏症易患SLE，表明C1q有助于维持耐受性。研究表明，C1q触发白细胞相关的igg样受体-1 （LAIR-1）激活，为理解C1q介导的耐受性机制提供了一些合理的线索。我们最近的研究发现，丁酸盐上调了LAIR-1的表达。本研究的目的是了解LAIR-1是如何调控的，以及它如何与C1q一起促进疾病预防。这些研究可能有助于确定SLE的潜在治疗靶点。因此，我们建议：了解c1q介导的LAIR-1激活机制。2. 了解调控LAIR-1表达的因素。3. 检验LAIR-1对狼疮模型的贡献。通过研究三个相关问题，我们将进一步定义SLE发病机制的生物学和临床新见解。

DESCRIPTION (provided by applicant): Systemic lupus erythematosus (SLE) is an autoimmune disease that has both genetic and nongenetic triggers. C1q deficiency is known to predispose to SLE, demonstrating that C1q helps maintain tolerance. Studies showing that C1q triggers leukocyte-associated Ig-like receptor-1 (LAIR-1) activation have yielded some reasonable clues for understanding tolerance mechanisms mediated by C1q. Our recent studies have revealed that butyrate up-regulates the expression of LAIR-1. The goal of this study is to understand how LAIR-1 is regulated and how it, together with C1q, contributes to disease prevention. These studies may help identify potential therapeutic targets in SLE. We therefore propose to: 1. Understand the mechanism of C1q-mediated LAIR-1 activation. 2. Understand factors regulating expression of LAIR-1. 3. Test the contribution of LAIR-1 to lupus models. By studying three relevant questions, we will further define new biological and clinical insights of SLE pathogenesis.