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.
Despite remarkable progress being made in controlling inflammation in chronic autoimmune disease, systemic lupus remains a challenging disease to treat. In order to develop a way to better regulate tolerance, we will focus on the regulation of inhibitory receptor, LAIR-1. Our goals are to investigate the relationship between LAIR-1 and disease pathogenesis in SLE and to address the clinical outcome of engaging LAIR-1.
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