T cell diversity during chronic inflammation

慢性炎症期间 T 细胞多样性

• 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
• 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

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.

项目摘要 胸腺来源的淋巴细胞（T细胞）是宿主防御的重要部分，并决定免疫应答的特异性。 对抗原的免疫反应。这项提案的总体目标是检查慢性炎症中的T细胞， 条件炎症可以由各种类型的效应T细胞的激活或免疫调节异常驱动。 然而，这些不同的T细胞亚群是否共享相同的TCR并识别调节性T细胞， 相同的抗原表位在很大程度上是未知的。此外，基因表达和克隆扩张之间的联系 在单细胞水平上，在肺的慢性炎症中尚未建立。我们计划表演单人- 晚期囊性纤维化（CF）肺病患者气道T细胞的细胞RNA测序 与非疾病对照相比，以填补这一知识空白。我们将使用CF作为模型来研究慢性 肺部的炎症状态我们假设慢性炎症CF气道中的T细胞具有明显的 与非疾病T细胞相比，不同的转录组学谱，并使用TCR分析，我们假设 在CF T细胞中将观察到增加的克隆扩增和17型免疫偏倚。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; 验证使用单细胞RNA测序鉴定的CF气道内T细胞的顶级候选基因。