Role of IL-13 and TGF-beta1 in the development of chronic rejection in solid organ transplantation

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Advances in post-transplant management of rejection and infection have tremendously improved patient survival following organ transplantation. Nevertheless, our understanding and treatment of chronic rejection has not significantly advanced in the last decades. One specific problem is the development of allograft fibrosis with the consequence of graft function loss. Previously, we could demonstrate the molecular events underlying tissue fibrosis. We showed that key players of the fibrotic program are IL-13 and TGF-β1. These two cytokines are connected through a recently identified IL-13 receptor, formerly thought to function only as a decoy receptor, IL-13Rα2, and this receptor is critical for the production of TGF-β1 and the onset of fibrosis. We hypothesise that the IL-13 – TGF-β1 interaction is responsible for the induction of allograft fibrosis and that interference with this interaction can prevent loss of organ function. We will now investigate the fibrotic program contributing to chronic allograft rejection following heart transplantation in mice. The aim of this research is to establish new treatment options for the prevention of allograft fibrosis to improve long-term transplant outcome.