T cell diversity during chronic inflammation

慢性炎症期间 T 细胞多样性

基本信息

批准号：
10558607
负责人：
Keven Mara Robinson
金额：
$ 7.36万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10558607
关键词：
Antibodies Antigen Receptors Antigens Bacteria Bronchoalveolar Lavage Fluid Candidate Disease Gene Cell Count Cell physiology Cells Chromium Chronic Clonal Expansion Collecting Cell Computer software Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Data Disease model Enzyme-Linked Immunosorbent Assay Epitopes Exons Expression Library Future Gene Expression Gene Mutation Genes Genomics Goals Hereditary Disease Heterogeneity Host Defense Human Immune Immune response Immunity Immunotherapeutic agent Individual Infection Inflammation Inflammatory Knowledge Learning Libraries Licensing Link Lung Lung Transplantation Lung diseases Lymphocyte Methodology Methods Modeling Molecular Profiling Monoclonal Antibody HuM291 Mononuclear Mutation Natural Killer Cells Organ Pathway Analysis Patients Phenotype Population Process Prospective, cohort study Proteins Pulmonary Cystic Fibrosis Recombinant Proteins Recovery Regulator Genes Regulatory Pathway Regulatory T-Lymphocyte Research Resources Reverse Transcriptase Polymerase Chain Reaction Rod Sampling Sorting Specificity Stains Structure of parenchyma of lung System T cell differentiation T-Cell Activation T-Cell Receptor T-Lymphocyte T-Lymphocyte Subsets T-cell diversity TCR Activation Technology Thymus Gland Time Transplantation Surgery Universities Validation Western Blotting airway epithelium antigen binding biobank chronic inflammatory disease cystic fibrosis airway cystic fibrosis patients effector T cell experimental study gene regulatory network genomic platform immune function novel therapeutics patient population polypeptide recruit single-cell RNA sequencing transcriptome transcriptomics

项目摘要

PROJECT SUMMARY Thymus-derived lymphocytes (T cells) are an essential part of host defense and determine the specificity of the immune response to antigens. The overall goal of this proposal is to examine T cells in a chronic inflammatory condition. Inflammation can be driven by activation of various types of effector T cells or dysregulation of regulatory T cells, however, whether these different subsets of T cells share the same TCR and recognize the same antigen epitope is largely unknown. Furthermore, the link between gene expression and clonal expansion at single cell level has not been established during chronic inflammation in the lung. We plan to perform single- cell RNA sequencing of T cells from the airways of patients with advanced cystic fibrosis (CF) lung disease compared to non-disease controls to fill this knowledge gap. We will use CF as a model to study chronic inflammatory states in the lung. We hypothesize that T cells in the chronically inflamed CF airway have distinctly different transcriptomic profiles compared to non-disease T cells, and using TCR analysis, we postulate increased clonal expansion and Type 17 immunity bias will be observed in CF T cells. Our research aims include: 1) To investigate T cell phenotypes, gene regulatory pathways, and antigenicity within the CF airway and (2) To validate top gene candidates of T cells within the CF airway identified using single-cell RNA sequencing.

项目概要胸腺来源的淋巴细胞（T 细胞）是宿主防御的重要组成部分，决定着免疫系统的特异性。对抗原的免疫反应。该提案的总体目标是检查慢性炎症中的 T 细胞健康）状况。炎症可能是由各种类型效应 T 细胞的激活或 T 细胞失调引起的。然而，调节性 T 细胞，这些不同的 T 细胞亚群是否共享相同的 TCR 并识别相同的抗原表位很大程度上是未知的。此外，基因表达和克隆扩增之间的联系在肺部慢性炎症期间尚未确定单细胞水平。我们计划执行单对晚期囊性纤维化 (CF) 肺病患者气道 T 细胞进行细胞 RNA 测序与非疾病控制相比，填补了这一知识空白。我们将使用 CF 作为模型来研究慢性病肺部的炎症状态。我们假设慢性炎症 CF 气道中的 T 细胞明显具有与非疾病 T 细胞相比，具有不同的转录组特征，并且使用 TCR 分析，我们假设 CF T 细胞中会观察到克隆扩张增加和 17 型免疫偏差。我们的研究目标包括： 1) 研究 CF 气道内的 T 细胞表型、基因调控途径和抗原性，以及 (2) 验证使用单细胞 RNA 测序识别的 CF 气道内 T 细胞的顶级候选基因。