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处理的进展极大地提高了器官移植后患者的存活率。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。一个特殊的问题是移植物纤维化的发展，其后果是移植物功能丧失。在此之前，我们可以演示组织纤维化的分子事件。这两种细胞因子通过新近发现的IL-13受体-IL-13R-β-2联系在一起，而IL-13R-α-2被认为是诱骗受体，该受体在转化生长因子-β-1的产生和纤维化的发生中起关键作用。我们假设IL-13-转化生长因子-β-1相互作用是导致同种异体移植肝纤维化的原因，干预这种相互作用可以防止器官功能的丧失。我们现在将研究导致小鼠心脏移植后慢性排斥反应的纤维化程序。这项研究的目的是建立预防同种异体移植肝纤维化的新的治疗方案，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.