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 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. The objective of this project is to mechanistically understand scavenger receptor A (SRA), an innate pattern recognition receptor primarily expressed in innate myeloid cells, in promoting excessive inflammation and bone erosion during RA development. Using clinically relevant mouse models, we showed that lack of SRA in mice resulted in reduced inflammation, characterized by decreased IL-1beta-expressing monocytic myeloid-derived suppressor cells (M-MDSCs),Th17 cells as well as Th1 cells following induction of collagen-induced arthritis. Additionally, SRA can promote Th17 cell triggered production of IL-1beta by M-MDSCs during the cellular interplays, which does not involve classical inflammasome activation. Furthermore, our proof-of-concept study showed that antibody blockade of SRA on M-MDSCs resulted in potent inhibition of M-MDSC differentiation into osteoclasts that can mediate bone loss. These data reveal a previously underappreciated autoimmune mechanism involving the myeloid cell-lymphocyte cross-talk that is regulated by SRA. Strategically targeting SRA to reduce inflammation and bone erosion may provide a novel approach to the treatment of RA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1202705
Entities
People
- Xiang-Yang Wang
Organizations
- Virginia Commonwealth University