Immune Mechanisms of Large-airway Lymphocytic Bronchitis

大气道淋巴细胞性支气管炎的免疫机制

• 批准号: 9254433
• 负责人: JOHN GREENLAND
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9254433
• 关键词: Acute; Affect; Antibody Response; Antibody titer measurement; Antigen-Presenting Cells; Award; Bioinformatics; Biometry; Biopsy; Bronchiolitis Obliterans; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; CD4 Positive T Lymphocytes; Caregivers; Caring; Cell Count; Cells; Characteristics; Chronic; Clinical Research; Clone Cells; Critical Care; Detection; Development; Early Diagnosis; Epithelial; Epithelial Cells; FOXP3 gene; Flow Cytometry; Foundations; Frequencies; Future; Goals; Greenland; Health; Helper-Inducer T-Lymphocyte; Human; IL2RA gene; Immune; Immune response; Immune system; Immunologist; Immunology; Immunophenotyping; Immunosuppression; Improve Access; International; Intervention; Intervention Trial; K-Series Research Career Programs; Lead; Lesion; Light; Liquid substance; Lung; Lung Transplantation; Lung diseases; Lymphocyte; Lymphocytosis; Medical; Mentors; Mentorship; Methods; Natural Killer Cells; Pathologic; Pathology; Patients; Performance; Phenotype; Physicians; Population; Prediction of Response to Therapy; Production; Prospective cohort; Publishing; Regulatory T-Lymphocyte; Research; Research Personnel; Research Support; San Francisco; Services; Severities; Specificity; Syndrome; T cell response; T-Lymphocyte; Techniques; Testing; Time; Transplant Recipients; Transplantation; Transplantation Immunology; Validation; Veterans; arm; authority; base; biomarker development; career; cell type; chemokine receptor; cohort; cytokine; cytotoxic; deep sequencing; experience; improved; isoimmunity; next generation; patient oriented research; peripheral blood; predicting response; prevent; programs; prospective; public health relevance; receptor expression; response; skills; tool; transcription factor; translational scientist

 DESCRIPTION (provided by applicant): This is an application for a Career Development Award (CDA-2) for Dr. John Greenland, a staff physician in the Pulmonary and Critical Care Section of the San Francisco VA Medical Service who is establishing himself as an investigator in patient-oriented research into the immunology of lung transplantation. This CDA-2 award will provide Dr. Greenland with the necessary support to accomplish the following goals: (1) to improve the understanding of predictors of chronic lung rejection, (2) to acquire theoretical and practical skills in bioinformatics and advanced T cell immunology, (3) to establish the mechanistic foundations for future interventional trials to improve post-lung transplant surveillance, and (4) to establish an independent clinical research career focused on lung transplantation immunology. To achieve these goals, Dr. Greenland has assembled a mentoring team consisting of (1) primary mentor Dr. George Caughey, an internationally respected authority in pulmonary immunology with a track record of mentoring translational researchers, (2) Dr. David Daikh, a recognized translational T cell immunologist, (3) Dr. Qizhi Tang, an expert in human transplant immunology; and (4) Dr. Jeffrey Golden, who has over 25 years of experience with clinical research in lung transplantation. Additionally, he will benefit from tutorials and mentorship from Drs. Nick Jewell, Scott Boyd, and Kirk Jones, in biostatistics, bioinformatics, and pathology, respectively; and research support from Drs. Lewis Lanier and Mark Ansel. The proposed research expands on Dr. Greenland's recently published findings that lymphocytic bronchitis (LB) on post-lung transplant surveillance biopsy predicts the development of chronic rejection in the form of bronchiolitis obliterans syndrome (BOS). The proposed study will establish a prospective cohort of lung transplant recipients to achieve the following specific aims: (1) determine the phenotype and specificity of infiltrating T cells in LB, (2) assess regulatory, humoral, and innate lymphocyte responses during LB, and (3) prospectively assess LB as a predictor of BOS. These studies will make use of next-generation flow cytometry and sequencing techniques to characterize immune responses in peripheral blood, airway brushings and biopsies, and bronchoalveolar lavage fluid from patients undergoing post-transplant surveillance bronchoscopy. A better understanding of LB may allow it to become an important biomarker for the development of BOS, while understanding LB in the context of the post-lung transplantation donor-specific immune response will lead to new tools for optimizing immunosuppression and inducing tolerance.

 描述（由申请人提供）： 这是约翰·格林兰博士（John Greenland）博士的职业发展奖（CDA-2）的申请。该CDA-2奖将为格陵兰博士提供必要的支持，以实现以下目标：（1）提高对慢性肺抑制预测指标的理解，（2）获得生物信息学和先进T细胞免疫学方面的理论和实践技能，（3），（3）建立对未来的介入式培训的机械基础，以建立施加后的施工后，以建立施加后的培训，以建立施用后置术，并（4）独立的（4）运输（4），（4）4）（4）（4）。免疫学。为了实现这些目标，格陵兰博士召集了一个由（1）主要心理团队组成的，乔治·科伊（George Caughey）博士是肺部免疫学领域的国际尊敬的权威，具有心理转化研究人员的记录，（2）David David Daikh博士，公认的翻译T细胞免疫学，（3）Qizhi Tang博士，一名人类人体传播的专家Qizhi Tang博士； （4）杰弗里·戈登（Jeffrey Golden）博士，他在肺部移植方面拥有超过25年的临床研究经验。此外，他将从博士的教程和心理中受益。尼克·杰维尔（Nick Jewell），斯科特·博伊德（Scott Boyd）和柯克·琼斯（Kirk Jones），分别在生物统计学，生物信息学和病理学中；和博士的研究支持。刘易斯·拉尼尔（Lewis Lanier）和马克·安塞尔（Mark Ansel）。拟议的研究扩展了格陵兰博士最近发表的发现，即淋巴细胞性支气管炎（LB）对肺部移植后监测活检预测了慢性抑制作用以支气管炎的形式发展为卵支气管炎的形式（BOS）。拟议的研究将建立一个前瞻性的肺移植受者队列，以实现以下特定目的：（1）确定LB中浸润T细胞的表型和特异性， （2）评估LB期间的调节，体液和先天淋巴细胞反应，（3）前瞻性评估LB作为BOS的预测指标。这些研究将利用下一代流式细胞仪和测序技术来表征外周血，气道刷子和活检中的免疫调查，以及来自接受移植后植物培养液支气管镜检查的患者的支气管肺泡灌洗液。更好地了解LB可以使其成为BOS开发的重要生物标志物，同时在肺部移植后供体特异性免疫反应的背景下了解LB，将为优化免疫抑制和诱发耐受性提供新的工具。