The Role of Lymphoid Neogenesis in the Maintenance of Lung Transplant Tolerance

淋巴新生在维持肺移植耐受中的作用

• 批准号: 10625536
• 负责人: Daniel Kreisel
• 金额: $ 37.59万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-12 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625536
• 关键词: Role; Lymphoid; Neogenesis; Maintenance; Lung

PROJECT SUMMARY / ABSTRACT Pulmonary transplantation remains the only available treatment for numerous patients, who suffer from end-stage lung disease. However, outcomes after lung transplantation continue to be substantially worse than those after transplantation of other organs. Current immunosuppressive strategies for lung transplant patients are based on protocols that have been successfully used for recipients of other organs. However, such approaches do not account for fundamental differences between immune responses to lung grafts and other commonly transplanted solid organs. Utilizing new mouse models of lung transplantation we have uncovered that tolerance to pulmonary grafts is regulated locally through interactions of immune cells within lymphoid aggregates that are newly formed in the graft. We have reported that disruption of immunoregulatory circuits in tolerant grafts results in the local activation of graft-infiltrating lymphocytes, which triggers rejection. This application proposes to study mechanisms how tolerance is maintained at the level of the graft microenvironment after pulmonary transplantation and will allow for the development of new therapies for lung transplant recipients.

项目摘要 /摘要 肺移植仍然是众多患者的唯一可用治疗方法 来自末期肺部疾病。但是，肺移植后的结果继续是 移植其他器官后比那些要差得多。当前的免疫抑制 肺移植患者的策略基于已成功使用的方案 对于其他器官的接收者。但是，这种方法并不能说明基本 免疫反应对肺移植物的免疫反应与其他通常移植的固体之间的差异 器官。利用新的肺移植鼠标模型，我们发现了对 肺移植物通过淋巴机内的免疫细胞的相互作用在局部调节 在移植物中新形成的聚集体。我们报告了这种破坏 耐受移植物中的免疫调节电路导致移植物浸润的局部激活 淋巴细胞，会触发排斥。该申请提出了研究机制 耐受性保持在肺移植后移植微环境的水平 并将为肺移植受者开发新疗法。