Therapeutic Targeting of Pattern Recognition Scavenger Receptor for Treatment of RA
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes irreversible joint damage and significant disability.The pathogenesis of RA is often associated with activation of immune cells and osteoclasts that cascade into a vicious cycle of inflammation and bone erosion. However, the fundamental mechanisms underlying how excessive inflammation and bone erosion develop and are sustained chronically in RA remain largely unknown. Using clinically relevant mouse models, we revealed that genetic ablation of scavenger receptor A (SRA, CD204), an innate pattern recognition receptor primarily expressed in innate myeloid cells, rendered mice fully protected from induction of collagen-induced arthritis. Lack of SRA also impairs pathogenic inflammatory responses in arthritic mice, characterized by significantly reduced IL-17A-expressing Th17cells known to be involved in the disease pathogenesis. Additionally, SRA is necessary for inflammatory myeloid-derived suppressor cells (MDSCs) to acquire a Th17-promoting capacity to drive excessive and dysregulated inflammation in autoimmune arthritis. We also show that arthritis-expanded MDSCs can stimulate the pro-osteoclastogenic activity in Th17cells, indicating a functional interplay between these two immune cell populations. These data suggest that SRA represents a previously unrecognized key regulator of RA development and may be potentially targeted for limiting immune pathology as well as for disease intervention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1123945
Entities
People
- Xiang-Yang Wang
Organizations
- Virginia Commonwealth University