Pathways Regulating Lung Transplant Tolerance.

调节肺移植耐受性的途径。

基本信息

批准号：
10424438
负责人：
Daniel Kreisel
金额：
$ 152.82万
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/10424438
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.

项目摘要/摘要肺移植仍然是许多患有终端的患者的唯一可用治疗方法肺部疾病。然而，肺移植后的结果仍然差得多与其他器官移植后相比。当前的肺免疫抑制移植患者基于为接受其他的患者开发的方案器官。但是，这种方法不会将肺的独特免疫学特征带入考虑与其他常见的器官有很大不同的考虑。利用新临床相关的肺移植小鼠模型我们发现了这种诱导和通过免疫的相互作用，在局部调节对肺移植的耐受性的维持移植物中的细胞。耐受的肺移植物会形成富集在维持静止状态的免疫调节细胞群体。该建议探讨了机制如何调节肺移植后如何调节耐受性。我们检查途径当耐受状态破坏时，会导致移植失败。从此应用中获得的见解将允许为肺移植患者制定新的治疗策略。