Pathways Regulating Lung Transplant Tolerance.

项目摘要/摘要 肺移植仍然是许多患者唯一可用的治疗方法，他们患有终末期肺移植。 肺部疾病的阶段。然而，肺移植后的结果仍然糟糕得多。 与其他器官移植后的患者相比。目前对肺的免疫抑制作用 移植患者是基于已经为接受其他移植的患者开发的方案 器官。然而，这种方法并不能将肺的独特免疫学特征带入 与其他常见的移植器官有很大不同的考虑。利用新的 临床相关的小鼠肺移植模型，我们已经发现诱导和 肺移植耐受性的维持是通过免疫相互作用在局部调节的 移植物内的细胞。耐受性肺移植形成富含 保持静止状态的免疫调节细胞群。这项提案探索了 肺移植后耐受性的调节机制。我们检查路径 当容忍状态被破坏时，这会导致移植失败。从该应用程序中获得的见解 将为肺移植患者开发新的治疗策略。

PROJECT SUMMARY/ABSTRACT Lung transplantation remains the only available treatment for many patients, who suffer from end- stage pulmonary disease. Outcomes after lung transplantation, however, continue to be far worse compared to those after transplantation of other organs. Current immunosuppression for lung transplant patients are based on protocols that have been developed for patients receiving other organs. However, such approaches do not take unique immunological features of lungs into consideration that differ substantially from other commonly transplanted organs. Utilizing new clinically relevant mouse models of lung transplantation we have uncovered that induction and maintenance of tolerance to pulmonary grafts is regulated locally through interactions of immune cells within the graft. Tolerant lung grafts develop tertiary lymphoid organs that are enriched in immunoregulatory cell populations that maintain a quiescent state. This proposal explores mechanisms how tolerance is regulated after pulmonary transplantation. We examine pathways that result in graft failure when the tolerant state is disrupted. Insights gained from this application will allow for the development of new therapeutic strategies for lung transplant patients.