A central role for the mesothelium in Restrictive Allograft Syndrome after lung transplantation

Chronic lung allograft dysfunction (CLAD) remains the major long term complication after lung transplantation.  Recently, a new clinical phenotype, restrictive allograft syndrome (RAS), is identified which affects 30% of CLAD patients and which results in a survival after diagnosis limited to 0.5-1 year. In this project, we hypothesize an important role for mesothelial cells and mesothelial mesenchymal transition (MMT) in RAS. Our aim is to investigate: 1/ the role and structural organization of mesothelial cells in RAS 2/ the pathophysiological mechanisms of mesenchymal infiltration with a focus on inflammation and immunosuppression and 3/ the effect of current and new therapeutic agents. Our approach is to work with explant lung tissue, mesothelial cell culture and our mice orthotopic lung transplant model. This study aims to better understand the impact and mechanism of pleural mesenchymal cells in RAS and how current and new treatment options can help to improve the long-term survival.