Effect of selective deletion of FAP expressing fibroblasts on the trafficking of T cells into the inflamed synovium. (360G-Wellcome-207112_Z_17_Z)

The main targets of rheumatoid arthritis (RA) treatments have previously been the leukocytes and cytokines they produce, however depleting these causes immunosuppression and infection by opportunistic disease. A mesenchymal cell marker, fibroblast activation protein (FAP) for constitutively active synovial fibroblasts in rheumatoid arthritis has been identified and found to be highly expressed in active disease with high levels correlated to a more aggressive disease presentation. Importantly in the inflammatory response, these cells are thought to be the key drivers of inflammation and joint damage in RA. It is possible that these cells regulate the recruitment of T cells into the joint and therefore their deletion prevents this accumulation, allowing resolution of inflammatory arthritis. This research has provided a promising target for new therapeutics. This project will analyse, by flow cytometry and immunofluorescence, the effect of deleting FAP+ fibroblasts within the inflamed joint. Specifically, the effect this has on the trafficking of T cells to the joint during experimental arthritis. The aim is to identify the differences in T cell types and populations that accumulate within the inflamed synovium between tissue samples. This will hopefully identify a possible mechanism of deleting RA synovial fibroblasts as a therapeutic target.