Human dendritic cell localization and anti-viral function in tissue sites

人树突状细胞在组织部位的定位和抗病毒功能

• 批准号: 10419871
• 负责人: Boris Reizis
• 金额: $ 29.29万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10419871
• 关键词: Anatomy; Animal Model; Antibody Response; Antigen Presentation; Antigens; B-Lymphocytes; Blood; Blood Circulation; COVID-19; Cell Compartmentation; Cell Count; Cell Lineage; Cell physiology; Cell surface; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Complement; Cross Presentation; Cytomegalovirus; Dendritic Cells; Elements; Environment; Flow Cytometry; Goals; Human; Human body; Immune; Immune response; Immunochemistry; Immunosuppressive Agents; Individual; Infection; Inflammation; Inflammatory; Influenza vaccination; Interferon Type I; Interferons; Link; Location; Maps; Organ; Organ Donor; Outcome; Pathogenicity; Patients; Phenotype; Population; Production; Resources; Role; Sampling; Sentinel; Shapes; Site; Spatial Distribution; T-Lymphocyte; TNF gene; Technology; Testing; Time; Tissue atlas; Tissues; Vaccination; Vaccines; Viral; Viral Physiology; Virus; Virus Diseases; adaptive immune response; adaptive immunity; cell type; cohort; cytokine; high dimensionality; human tissue; influenza infection; insight; lymphoid organ; monocyte; multiple sclerosis patient; pathogen; programs; response; single-cell RNA sequencing; transcriptomics; vaccine immunogenicity

PROJECT 2: PROJECT SUMMARY Dendritic cells (DCs) are key immune sentinels that link innate recognition to adaptive immunity against pathogens, thereby initiating T and B cell responses. The DC lineage comprises two major subsets, type I interferon-producing plasmacytoid DCs (pDCs) and antigen-presenting conventional or classical DCs (cDCs). The exact subset composition and functional state of DC populations is specific for each organ/tissue, reflecting unique local immune environments. The parameters of DC function that correlate with protective versus pathogenic responses are still poorly understood. Furthermore, the location and functionality of DC populations in tissues and lymphoid organs has not been interrogated within the entire human body. In the first cycle of the project, we found that human pDCs respond differently to free viruses and virus-infected cells; compared to the former, the response to the latter is characterized by sustained production of type I and type III interferons and diminished production of inflammatory cytokines. The overall goal of the current project is a comprehensive characterization of human DC composition and function, specifically as it relates to immune responses to antiviral vaccines. We hypothesize that the type of pDC response (interferon-focused vs inflammatory cytokine-focused) is an important parameter of anti- viral/anti-vaccine immune responses that may correlate with and/or predict protective T cell and antibody responses. To test this notion, in Aim 1 we will build a universal reference map of pDC activation and test the ability of pDCs to mount interferon-focused and polyfunctional responses in subjects undergoing vaccination against influenza or COVID-19. We further posit that DC functionality may be shaped by specific tissue environments within the same individual. To explore this, in Aim 2 we will use high-dimensional immunochemistry to identify the location and cellular interactions of DC subsets in tissues and lymphoid organs, and combine the results with single-cell transcriptomics and the analysis of cytokine responses. Collectively, these studies would yield a comprehensive view of the composition, tissue diversity and functionality of the human DC compartment. They would also provide insights into the role and mechanism of cytokine responses by DCs in protective immune responses to virus infections.

项目2：项目总结