Molecular Control of Plasmacytoid Dendritic Cell Development and Function

浆细胞样树突状细胞发育和功能的分子控制

基本信息

批准号：
10207413
负责人：
Boris Reizis
金额：
$ 56.22万
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：
2007
资助国家：
美国
起止时间：
2007-12-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10207413
关键词：
Address Antiviral Response Autoimmune Diseases Autoimmune Responses Autoimmunity Award Bone Marrow CRISPR/Cas technology Cell Differentiation process Cell Line Cell Lineage Cell physiology Cells Cellular biology Coupled Dendritic Cells Development E protein Enhancers Evolution Gene Expression Gene Expression Profile Genes Genetic Screening Genetic Transcription Goals Heterogeneity Homeostasis Human Immune Immune response Immunotherapy In Vitro Infection Interferon Type I Interferon-alpha Interferons Mediator of activation protein Methods Molecular Mus Nucleic Acids Pathway interactions Phenotype Play Production Property Regulation Regulatory Element Role Systemic Lupus Erythematosus T cell factor 4 TCF7L2 gene Testing Therapeutic Toll-like receptors Transcriptional Regulation Virus Work adaptive immune response base cell type chemokine cytokine genetic analysis genetic approach hematopoietic differentiation high dimensionality human disease immunopathology in vivo in vivo evaluation leukemia novel progenitor response single cell analysis stem cells therapeutic target transcription factor transcriptomics translational approach

项目摘要

ABSTRACT Plasmacytoid dendritic cells (pDCs) rapidly secrete type I interferon (interferon α/β, IFN) in response to virus-derived nucleic acids, facilitating both innate and adaptive antiviral responses. Conversely, aberrant IFN production by pDCs is associated with autoimmune diseases, establishing pDCs as important emerging therapeutic targets. The overall goal of this project is to elucidate the molecular control of pDCs lineage, including its development, homeostasis and function in various immune responses. In the previous award cycles, we have identified E protein transcription factor TCF4 (E2-2) and several other factors as important regulators of pDC development. The proposed work will build upon these findings to address major unanswered questions in pDC biology. In Aim 1, we will use high-dimensional single-cell analysis methods to characterize the stage and regulation of pDC lineage specification, as well as the functional heterogeneity of mature pDCs. In Aim 2, we will use genetic approaches to dissect transcriptional control and regulation of the unique IFN-producing capacity of pDCs. Collectively, the proposed studies should yield a comprehensive molecular view of pDC development and function, paving the way for therapeutic approaches focused on this cell type.

抽象的浆细胞样树突状细胞 (pDC) 快速分泌 I 型干扰素（干扰素 α/β，IFN）以响应病毒衍生的核酸，促进先天性和适应性的离线、异常的抗病毒反应。 pDC 产生的 IFN 与自身免疫性疾病相关，因此将 pDC 确立为重要的新兴疾病该项目的总体目标是阐明 pDC 谱系的分子控制，包括其发育、稳态和在各种免疫反应中的功能。循环中，我们已经确定了 E 蛋白转录因子 TCF4 (E2-2) 和其他几个重要的因子拟议的工作将基于这些发现来解决主要问题。在目标 1 中，我们将使用高维单细胞分析方法。表征 pDC 谱系规范的阶段和调控以及功能异质性在目标 2 中，我们将使用遗传方法来剖析成熟 pDC 的转录控制和调节。总的来说，拟议的研究应该得出 pDC 独特的 IFN 产生能力。 pDC 发育和功能的全面分子视角，为治疗铺平道路方法集中于这种细胞类型。