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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01AR065506-01
Application #
8618460
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Mancini, Marie
Project Start
2014-09-16
Project End
2019-08-31
Budget Start
2014-09-16
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$127,710
Indirect Cost
$9,460
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030