PILRα negatively regulates mouse inflammatory arthritis
Yonglian Sun1, Patrick Caplazi2, Juan Zhang1
1Department of Immunology, Genentech, South San Francisco, CA 94080;
Journal of Immunology (Baltimore, Md. : 1950)
|June 18, 2014
Summary
Paired Ig-like type 2 receptor alpha (PILRα) is elevated in rheumatoid arthritis and drives inflammation. Inhibiting PILRα reduces arthritis severity, suggesting it’s a key target for treating autoimmune diseases.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Paired Ig-like type 2 receptors (PILR)α and PILRβ are coexpressed on myeloid cells.
- PILRα acts as an inhibitory receptor, while PILRβ is an activating receptor.
Purpose of the Study:
- To investigate the role of PILRα and PILRβ in rheumatoid arthritis (RA).
- To determine if PILRα can be a therapeutic target for RA.
Main Methods:
- Analysis of PILRα and PILRβ expression in human RA synovial tissue.
- Assessment of disease severity and cytokine production in Pilrα(-/-) mice.
- Evaluation of anti-PILRα monoclonal antibody (mAb) treatment in mouse arthritis models.
Main Results:
- PILRα, but not PILRβ, is upregulated in human RA synovial tissue and correlates with inflammatory cell infiltration.
- Pilrα(-/-) mice exhibit increased pathogenic cytokine production and exacerbated autoimmune arthritis.
- Anti-PILRα mAb treatment ameliorates inflammation and suppresses proinflammatory cytokine production in mouse arthritis models.
Conclusions:
- PILRα plays a critical role in promoting inflammation in autoimmune arthritis.
- PILRα represents a potential therapeutic target for dampening inflammatory responses in RA.
