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Modulation of Viral Antigen Presentation in the Lung

肺部病毒抗原呈递的调节

基本信息

批准号：
10436633
负责人：
Anna Karolina Palucka
金额：
$ 49.83万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-02 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10436633
关键词：
2019-nCoV 3-Dimensional Acute Address Administrative Supplement Adult Affect Age Alternative Splicing Antigen Presentation Antigens Antiviral Response Autoimmune Diseases Award B-Lymphocytes Bacteria Biology Biomedical Engineering Blood Cells COVID-19 COVID-19 patient Cell Line Cell model Cell physiology Cells Cellular biology Child Childhood Childhood Asthma Clinical Code Cohort Effect Communication Complement Complex Computational Biology Computer Analysis Coronavirus Data Set Dendritic Cells Dimensions Disease Environment Environmental Risk Factor Epithelial Epithelial Cells Family Funding Future Generations Genes Genetic Transcription Genomics Goals Human Immune Immune System Diseases Immune response Immune system Immunologics Immunology Immunology procedure Individual Infant Infection Inflammation Influenza Interferon Type I Interferons Interleukin-1 Invaded Leukocytes Long COVID Lung Lung diseases Lymphocyte Lymphoid Cell Malignant neoplasm of lung Messenger RNA Molecular Mucous Membrane Natural Immunity Parents Pathway interactions Patients Pediatric cohort Peptides Peripheral Peripheral Blood Mononuclear Cell Phenotype Production Protein Isoforms Proteins Proteomics Public Health RNA RNA Splicing Recording of previous events Research Research Project Grants Respiratory syncytial virus Ribonucleoproteins SARS-CoV-2 infection Sampling Severity of illness Shapes Small Nuclear RNA Specificity Spliceosomes Structure Structure of parenchyma of lung Surface Systemic Lupus Erythematosus T cell response T-Lymphocyte Technology The Jackson Laboratory Tissues Transcript Vaccines Viral Antigens Viral Load result Viral Respiratory Tract Infection Virus Virus Diseases Work adaptive immune response adaptive immunity antiviral immunity base bioprinting cell type cohort comorbidity coronavirus disease design detection method follow-up human model human tissue immune activation immune function imprint improved outcome influenzavirus innovative technologies insight lung microbiome mRNA Precursor mRNA sequencing microbiome microbiota monocyte multidisciplinary novel pathogen pediatric patients programs proteogenomics respiratory virus response sensor single-cell RNA sequencing symptomatic COVID-19 technology development tool transcriptome transcriptome sequencing tumor virtual

项目摘要

PROJECT SUMMARY (FUNDED PARENT AWARD, U19AI142733) We propose a U19 Cooperative Center on Human Immunology at The Jackson Laboratory (JAX CCHI) to elucidate the innate immune networks that shape adaptive immune responses to respiratory viral infections in the human lung. Epithelial barriers lie at the interface between host and environment, where they sense invading pathogen. Dendritic cells (DCs) present pathogen-derived antigens to T and B cells to induce immune responses. However, the impact of the human lung tissue environment on DC and other cells, such as the newly identified innate lymphoid cell (ILC) family, as well as bacteria-reactive MAIT cells, is not completely understood. An understudied environmental factor is the lung microbiome. Microbiota are known to critically modulate the function of immune cells, particularly at mucosal surfaces, but how this occurs in the lung is not fully addressed. The JAX CCHI seeks to address these critical questions using a multi-disciplinary experimental approach that will integrate immunology with epithelial cell biology along with genomic, cellular, functional and microbiome parameters identified in human lung tissues. Our overarching hypothesis is that the quality and magnitude of mucosal T cell responses to respiratory viral infections are determined by the cross- talk between microbiota, epithelial cells and leukocytes. To address this hypothesis, we structured the JAX CCHI around two integrated research projects focused on basic immunological mechanisms of lung antiviral immunity; a technology development project that will create sophisticated cellular models leveraging 3D bioprinting, gene editing tools and microbiome-immune assays to support project objectives; a sample core for storage and distribution of human tissues; and a microbiome core for specialized microbiome profiling, cultivation, and computational analysis. Our Center will bring together clinicians with experts in lung immunology, the microbiome, bioengineering, genomics and computational biology to achieve our goals and maximize the potential of this research. An administrative core will provide coordination, communication and oversight for the program. The goals of this CCHI are to: 1) Understand how the networks of epithelial cells and immune cells in the human lung regulate innate and adaptive immunity to respiratory viruses; 2) Define how inflammation driven by the microbiome dictates the steady state of tissue, i.e., immune set-point; 3) Determine if and how this immune set- point is altered in two pulmonary diseases, childhood asthma and adult lung cancer, which have a major impact on public health; and 4) Develop innovative technologies to model human lung-immune dynamics and elucidate molecular mechanisms, cell types and pathways key to lung antiviral responses. Impact: Through studies focused on the sensors, inducers and modulators of antiviral immunity in the human lung, our CCHI will contribute insights that could help improve outcomes for infectious and other immune diseases that originate in or secondarily impact the lung.

项目总结（资助父母奖，u19ai142733）