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Novel genetic tools for the analysis of plasmacytoid dendritic cell function in vivo

用于分析体内浆细胞样树突状细胞功能的新型遗传工具

基本信息

批准号：
9975706
负责人：
Boris Reizis
金额：
$ 21.19万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-10 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975706
关键词：
Address Animals Antigen Presentation Antiviral Response Autoimmune Diseases Biological Models CRISPR/Cas technology Cell physiology Cells Clustered Regularly Interspaced Short Palindromic Repeats Communities Cross Presentation Dendritic Cells Enterobacteria phage P1 Cre recombinase Epithelial Cell Aggregation and Separation Feedback Gene Expression Gene Targeting Genes Genetic Genetic Recombination Genetic Transcription Goals Green Fluorescent Proteins Hematopoietic stem cells Immune Immune response Immunologics Immunologist Immunotherapy Insulin-Dependent Diabetes Mellitus Interferon Type I Interferon-alpha Interferons Knock-in Mouse Lupus Mediating Mediator of activation protein Modeling Molecular Molecular Analysis Mus Natural Immunity Nucleic Acids Play Production Proteins Reporter Role Scleroderma Specificity System Systemic Lupus Erythematosus Testing Tissues Toll-like receptors Virus Virus Diseases Visualization adaptive immune response cell type chemokine cytokine immunopathology in vivo macrophage novel protein expression receptor response tool

项目摘要

ABSTRACT Plasmacytoid dendritic cells (pDCs) represent a distinct innate immune cell type capable of rapid and massive production of type I interferon in response to viruses. pDCs play an important role in both innate and adaptive immune responses to viral infections, whereas aberrant activation of pDCs contributes to autoimmune diseases such as systemic lupus erythematosus. Major questions about the role and molecular basis of pDC function still remain unanswered, largely due to the absence of pDC-specific Cre deleter and fluorescent reporter strains. The overall goal of this project is to develop novel genetic tools for functional analysis of pDCs. In Aim 1, we will use a candidate pDC-specific gene as a driver to express Cre recombinase in pDCs in vivo. We will examine the specificity and efficiency of Cre recombination in the resulting strain and use it in a proof-of-principle gene targeting in vivo. In Aim 2, we will use the same approach to generate a pDC-specific fluorescent reporter strain and use it to explicitly visualize pDC in tissue sections. Collectively, these studies address a major unmet need for model systems to study pDC function, and therefore would facilitate in vivo studies of innate immunity.

摘要浆细胞样树突状细胞（pDC）代表一种独特的先天性免疫细胞类型，其能够快速和特异性地诱导免疫应答。大量生产I型干扰素以应对病毒。pDC在先天免疫和免疫应答中发挥重要作用。和对病毒感染的适应性免疫应答，而pDC的异常激活有助于自身免疫性疾病，如系统性红斑狼疮。关于作用和分子的主要问题 pDC功能的基础仍然没有答案，主要是由于缺乏pDC特异性Cre删除剂，荧光报告菌株。该项目的总体目标是开发新的基因工具， pDC的分析。在目标1中，我们将使用候选pDC特异性基因作为驱动基因来表达Cre 重组酶在pDC中的表达。我们将研究Cre重组的特异性和效率，并将其用于体内基因靶向的原理验证。在目标2中，我们将使用相同的一种产生pDC特异性荧光报告菌株并使用其明确可视化pDC的方法，组织切片。总的来说，这些研究解决了模型系统研究pDC的主要未满足需求功能，因此将有助于先天免疫的体内研究。