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.
This project aims to:
M1: Established cell sorting protocol to sort all 4 SF subtypes – at 2 months
M2: Functional differences between SF subtypes assessed – at 6 months
M3: Impact of CXCL14 + and POSTN + SF on other cell types assessed – at 12 months
During the stay at the host center, the fellow will work together with a patient buddy. At the beginning and every three months, one-to-one meetings will be organized to discuss the project and its progress (virtual and/or visits to the lab).