The influence of joint-specific stroma on arthritis development and outcome

We could show that synovial fibroblasts significantly differ between different joint locations in their epigenome, transcriptome and function. We hypothesize that the differences in these local cells of the joints substantially influence the inflammatory response, the influx of immune cells, the resolution of inflammation and thus disease outcome and therapeutic response. To test this hypothesis, we analyze joint-specific differences in the inflammatory and anti-inflammatory response using histological and single cell molecular analysis and try to identify the key regulators of joint-specific inflammatory signaling pathways.

Involved team members

• Muriel Elhai
• Miranda Houtman
• Raphael Micheroli
  
  

Funded by

• Iten-Kohaut-Foundation
  
• Novartis Foundation for medical-biological research
• MLR Foundation
  
  

Relevant publications

• Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H, Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C. Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions. Nat. Commun. 8, 14852 doi: 10.1038/ncomms14852 (2017)
• Ospelt C, Frank-Bertoncelj M. Why location matters – site-specific factors in rheumatic diseases. Nat Rev Rheumatol. 2017 Jul;13(7):433-442. doi: 10.1038/nrrheum.2017.96.