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

基本信息

批准号：
10197016
负责人：
Daniel Kreisel
金额：
$ 38.69万
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/10197016
关键词：
Allogenic Antibodies B-Cell Activation B-Lymphocytes Binding Bronchus-Associated Lymphoid Tissue CCL17 gene CCL22 gene CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cell Differentiation process Cells Chronic Clinic Data Development FOXP3 gene Generations Graft Rejection Graft Tolerance Heart Transplantation Helper-Inducer T-Lymphocyte ITGAX gene Immune Immune response Immunosuppression Impairment Infection Infiltration Interferon Type II Kidney Transplantation Knowledge Laboratories Lung Lung Transplantation Lung diseases Lymphocyte Lymphoid Maintenance Mediating Natural Killer Cells Neutrophilic Infiltrate Organ Outcome Pathogenesis Pathway interactions Patients Pattern Play Population Procedures Production Protocols documentation Pseudomonas aeruginosa Pseudomonas aeruginosa infection Refractory Regulation Regulatory Pathway Reporting Research Role Solid T-Lymphocyte Techniques Tissue Transplantation Tissues Transplant Recipients Transplantation Transplantation Tolerance Work airway epithelium antibody-mediated rejection base chemokine clinically relevant donor-specific antibody eosinophil experience extracellular immunoregulation improved outcome liver transplantation lung allograft macrophage monocyte mouse model neutrophil novel novel therapeutics pathogen prevent recruit response therapy development treatment choice

项目摘要

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.

项目概要/摘要对于许多遭受痛苦的患者来说，肺移植仍然是唯一可用的治疗方法来自终末期肺部疾病。然而，肺移植后的结果仍然比其他器官移植后的情况要差很多。目前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受者。然而，这些方法并没有考虑到根本性的问题。对肺移植物和其他常见移植实体的免疫反应之间的差异器官。利用新的肺移植小鼠模型，我们发现了对肺移植的耐受性肺移植物通过淋巴内免疫细胞的相互作用进行局部调节移植物中新形成的聚集体。我们已经报告称，耐受移植物中的免疫调节回路导致移植物浸润的局部激活淋巴细胞，从而引发排斥反应。该申请旨在研究如何肺移植后移植微环境的耐受性得以维持并将允许为肺移植受者开发新疗法。