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Novel transcription factors modulating the development and function of pDCs and pDC-related cells

调节 pDC 和 pDC 相关细胞发育和功能的新型转录因子

基本信息

批准号：
10414818
负责人：
Juliana Idoyaga
金额：
$ 19.87万
依托单位：
STANFORD UNIVERSITY
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：
2021-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10414818
关键词：
Binding Biological Assay Cell Lineage Cell Maintenance Cell Proliferation Cell physiology Cells Charge Chromatin Collaborations Data Dendritic Cells Development Disease Fibrinogen Gene Expression Genetic Genetic Transcription Genomics Goals Human Human Cell Line ID2 gene Immune Immune response Individual Innate Immune Response Interferon Type I Interferons Knockout Mice Light Maintenance Modeling Mus Natural Killer Cells Outcome Play Regulation Research Role Site T-Cell Activation T-Lymphocyte TCF7L2 gene Testing Therapeutic Tissues Transcriptional Regulation Transposase Viral Virus Virus Diseases base cell type conditional knockout genome-wide high dimensionality immunoregulation innate immune function mouse model new therapeutic target novel overexpression pathogen programs rational design recruit response therapeutic development transcription factor

项目摘要

ABSTRACT Plasmacytoid dendritic cells (pDCs) and pDC-related cells are developmentally related innate immune cells capable of performing multiple functions essential for successful antiviral immune responses, including type I interferon secretion and T cell activation. The identity, i.e., development and function, of pDCs and pDC-related cells is controlled by the precise interaction of transcription factors (TFs). Tight regulation of transcriptional programs is essential to promote the appropriate response to pathogens while avoiding damage to healthy tissues. Thus, it is critical to unravel the transcriptional regulation of pDCs and pDC-related cells. Using a high- dimensional unbiased approach, we have recently discovered two conserved TFs that are specific and highly active in pDCs and pDC-related cells but not in other DC subsets. In two specific aims, we propose to explore the role of these TFs in determining the development and function of pDCs and pDC-related cells. To achieve our goal, we will take advantage of novel conditional knockout mouse models, transcription factor- overexpressing human cell lines, and high-dimensional approaches already established in our lab. We anticipate that findings from this proposal will bring into light novel mechanisms of transcriptional regulation that result in the positive outcome of innate immune responses against viruses. Importantly, our integrated approach will incorporate analyses of both mouse and human DCs; thus, it can reveal features that are conserved between species. This proposal has the potential to impact the rational design of therapeutic strategies by exploring regulatory programs determining the identity of key antiviral innate cells.

摘要