Characterization of Synovial Fibroblast Subtypes

Disease modifying anti-rheumatic drugs have revolutionized RA therapy, expanded life expectancy, and dramatically improved the quality of patients' lives. However, it is estimated that a significant number of patients display inadequate response, whereas others experience severe side effects. As evidence grows that RA patients with a "fibroid pathotype" respond less effectively to treatment, the need to develop therapeutic targets for influencing the activated stroma increases. Previous studies have highlighted the potential role of four distinct synovial fibroblast subtypes in the propagation of RA inflammation, warranting further investigation. This project aim is to further explore the functional differences of the synovial fibroblast subtypes and assess whether POSTN+ SF and CXCL14+SF are functional antagonists with opposite roles in the inflammatory process in RA. Furthermore, we aim to elucidate the spatial distribution of the fibroblast subtypes as well as their interaction with immune cells in the microenvironment of the synovial tissue from RA patients. Our approach would provide insight into the pathogenic role of the stroma and the different fibroblast subtypes and could be the trigger for uncovering novel therapeutic targets.