Mechanisms of tissue regeneration of the synovial membrane during resolution of inflammation

• Applicant: Dr. Simon Rauber
• Subject Area: Rheumatology ; Immunology ; Medical Informatics and Medical Bioinformatics
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568819271

Arthritis is a long-lasting disease caused by inflammation. The diseases mainly affects the joints and bones. Strategies to supress the immune system, which triggers the inflammation, have been extensively studied and are used in clinics. The problem, however, is that these therapies cannot stop the inflammation forever and do not allow the tissue to regenerate and to heal. In our earlier work, we showed that activating certain immune cells in the joint can reduce inflammation. We also found that a type of tissue cell called fibroblast can help to reduce inflammation by activating these immune cells. Fibroblasts can have several phenotypes. CD200+ fibroblasts (a type of fibroblast expressing the protein CD200) can activate ILC2s (an immune cell). ILC2s trigger an anti-inflammatory response in arthritis. However, to fully resolve the inflammation, the tissue needs to return to a healthy state. This means that the structural organisation of the tissue, which is lost during inflammation, must to be restored. While our study looked at how the arthritis gets better, we also found that CD200+ fibroblasts do not contribute to the repair the joint tissue. Instead, we have found that another subtype of fibroblasts might be very important in this process. However, this assumption has yet to be definitively. We therefore plan to investigate the synovial fibroblasts during the transition from inflammation to healing to understand how this new fibroblast subtype emerges and repairs tissue. We plan to: 1. We want to check if biomarkers for tissue remodelling are present in the synovial tissue and blood of people with active arthritis or arthritis in remission. We will look at how these biomarkers are related to disease severity and tissue destruction. 2. We will also investigate whether the newly identified fibroblast subtype helps to maintain the structure of the tissue in the joint. We want to identify the factors that stimulate the production of tissue remodelling enzymes. 3. We will also study if this newly identified fibroblast subtype could be a target for drugs. We will do experiments to stop it working in an arthritis model. This will help to find new ways to treat arthritis.

• DFG Programme: Research Grants