Pathways Regulating Lung Transplant Tolerance.

调节肺移植耐受性的途径。

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要对于许多患有终末期心脏病的患者来说，肺移植仍然是唯一可用的治疗方法。阶段肺部疾病。然而，肺移植后的结果仍然更糟与其他器官移植后的结果相比。目前肺部免疫抑制移植患者基于为接受其他治疗的患者制定的方案器官。然而，此类方法并未将肺部独特的免疫学特征纳入研究范围。与其他常见移植器官有很大不同的考虑因素。利用新我们发现，在临床相关的肺移植小鼠模型中，诱导和对肺移植物耐受性的维持是通过免疫相互作用进行局部调节的移植物内的细胞。耐受性肺移植物会发育出富含维持静止状态的免疫调节细胞群。该提案探讨了肺移植后耐受性的调节机制。我们检查路径当耐受状态被破坏时，会导致移植失败。从这个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。