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

移植后排斥反应和感染管理的进步极大地提高了器官移植后患者的生存率。然而，在过去的几十年里，我们对慢性排斥反应的理解和治疗并没有显著的进步。一个具体的问题是同种异体移植物纤维化的发展与移植物功能丧失的后果。以前，我们可以证明组织纤维化背后的分子事件。我们发现纤维化程序的关键参与者是IL-13和TGF-β1。这两种细胞因子通过最近发现的IL-13受体连接在一起，该受体以前被认为仅作为诱饵受体IL-13Rα2起作用，该受体对TGF-β1的产生和纤维化的发生至关重要。我们假设IL-13 - TGF-β1相互作用是诱导同种异体移植物纤维化的原因，干扰这种相互作用可以防止器官功能的丧失。我们现在将在小鼠心脏移植后研究纤维化程序对慢性同种异体移植排斥反应的影响。本研究的目的是为预防同种异体移植纤维化建立新的治疗选择，以改善长期移植结果。

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.