Summary
This research project aims to define how the T-bet transcription factor influences synovial B cell states, mediates B cell-driven bone effects, and coordinates B cell pathogenic functions in rheumatoid arthritis (RA) target tissue, contributing to joint erosion and synovial inflammation.
What they want
The central goal is to understand the role of T-bet in promoting pathogenic B cell functions in the RA synovium. This involves investigating how T-bet influences B cell states, mediates B cell-driven bone effects on osteoclasts (OCs) and osteoblasts (OBs), and coordinates B cell pathogenic functions in RA target tissue. The project will determine the mechanisms by which B cell T-bet promotes RA joint erosion, assess how T-bet B cells impact RA synovial monocyte activation, and examine the role of T-bet in B cells during inflammatory-erosive arthritis in mice.
Deliverables
- Mechanisms by which B cell T-bet promotes RA joint erosion
- Assessment of T-bet B cell impact on RA synovial monocyte activation
- Examination of T-bet's role in B cells during inflammatory-erosive arthritis in mice
Technical requirements
- Deeply characterized RA patient cohorts
- High-resolution single cell transcriptomic analysis of joint target tissue
- Spatial analysis of joint target tissue
- Novel animal models to track T-bet B cells
- Selective and conditional deletion of T-bet in B cells of mice with collagen induced arthritis
- Preclinical studies
- Translational studies
