Therapeutic Targeting of Pattern Recognition Scavenger Receptor for Treatment of Rheumatoid Arthritis
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes irreversible joint damage and significantdisability. The pathogenesis of RA is often associated with activation of immune cells and osteoclasts that cascade into avicious cycle of inflammation and bone erosion. However, the fundamental mechanisms underlying how excessiveinflammation and bone erosion develop and are sustained chronically in RA remain largely unknown. Using clinically relevantmouse models, we revealed that genetic ablation of scavenger receptor A (SRA, CD204), an innate pattern recognitionreceptor primarily expressed in innate myeloid cells, rendered mice fully protected from induction of collagen-induced arthritis.Lack of SRA abolished cartilage erosion of articular surface, and synovial hyperplasia in the articular cavity. Monocytic MDSCs(M-MDSCs) can be important precursors of OCs given their inherent capability to different into OCs. Additionally, SRA wasshown to function as a critical molecular factor governing OC differentiation from M-MDSCs, which may be its previouslyunrecognized activity in modulating the RANKL signaling. These data indicate that SRA is involved in osteoclastogenicprocesses of autoimmune arthritis and provide a scientific rationale for targeting SRA to potentially mitigate the symptoms ofRA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1158159
Entities
People
- Xiang-Yang Wang
Organizations
- Virginia Commonwealth University