Pathways Regulating Lung Transplant Tolerance.

调节肺移植耐受性的途径。

• 批准号: 10197013
• 负责人: Daniel Kreisel
• 金额: $ 156.18万
• 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/10197013
• 关键词: Acute; Affect; Allograft Tolerance; Area; Bronchiolitis; Bronchus-Associated Lymphoid Tissue; Cells; Chronic; Collaborations; Cues; Development; Event; Functional disorder; Funding; Graft Rejection; Graft Survival; Human; Immune; Immune response; Immunologic Factors; Immunologics; Immunosuppression; Inflammatory; Knowledge; Laboratories; Light; Lung; Lung Transplantation; Lung diseases; Lymphoid; Maintenance; Mediating; Mediator of activation protein; Methods; Molecular; Organ; Organ Transplantation; Outcome; Pathologic; Pathway interactions; Patient imaging; Patients; Physicians; Physiological; Population; Protocols documentation; Regimen; Reproducibility; Research; Role; Scientist; Survival Rate; Tissues; Transplant Recipients; Transplantation; Transplantation Tolerance; Work; adaptive immune response; antibody-mediated rejection; base; clinically relevant; graft failure; imaging approach; immunoregulation; improved outcome; innovation; insight; intravital imaging; lung allograft; mouse model; novel; novel therapeutic intervention; novel therapeutics; programs; synergism; tertiary lymphoid organ

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.

项目总结/摘要 肺移植仍然是许多患者唯一可用的治疗方法，他们患有终末期肺结核。 阶段性肺病。然而，肺移植后的结果仍然很糟糕 与其他器官移植后相比。当前肺部免疫抑制 移植患者是基于已经为接受其他器官移植的患者开发的方案。 机关然而，这种方法没有将肺部独特的免疫学特征纳入其中， 考虑与其他常见的移植器官有很大不同。利用新 临床相关的小鼠肺移植模型，我们已经发现， 对肺移植物耐受性的维持通过免疫系统的相互作用局部调节， 移植物内的细胞。耐受性肺移植物发育三级淋巴器官，其富含 免疫调节细胞群维持静止状态。该提案探讨了 肺移植后耐受性的调节机制。我们研究了 当耐受状态被破坏时导致移植失败。从该应用程序中获得的见解 将允许为肺移植患者开发新的治疗策略。