Heterogeneity and cellular hierarchy of lung cDC2

肺 cDC2 的异质性和细胞层次

基本信息

批准号：
10665348
负责人：
Gye Young Park
金额：
$ 23.99万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-06 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10665348
关键词：
Acute Address Adopted Adoptive Transfer Affect Allergic Alveolar Macrophages Animal Model Aspergillus Attenuated Bioinformatics Blood CX3CR1 gene Categories Cell Count Characteristics Collaborations Data Dendritic Cells Development Disease Extrinsic asthma Gene Expression Heterogeneity Hypersensitivity ITGAX gene Immune response Immunity Inflammation Knowledge Lung Lung diseases Lymphoid Cell Malignant Neoplasms Maps Mediating Modeling Mouse Strains Mus Mycoses Myeloid Cells Natural Immunity Operative Surgical Procedures Parabiosis Parasitic infection Play Population Pulmonary Inflammation RNA Reporter Research Rest Role Specificity Stains Techniques Testing adaptive immunity airway inflammation cell type high dimensionality insight interest mouse model novel single-cell RNA sequencing tool transcriptomic profiling transcriptomics

项目摘要

Abstract Dendritic cells (DCs) play a fundamental role in bridging innate and adaptive immunity. Among DC subtypes, conventional DC2 (cDC2) are pivotal in multiple diseases including allergy, fungal & parasite infection, and cancer. However, studying cDC2 has been challenged by the small cell number and a lack of the subset- specific animal model. To better understand the characteristics and roles of cDC2 subsets, we have utilized the cutting-edge, RNA-based high-throughput transcriptomic profiling technique known as single cell RNA- sequencing (scRNA-seq). This approach has enabled us to better understand lung cDC2 in terms of diversity and cellular hierarchy. Our preliminary data indicate that lung cDC2 can be categorized into 6 distinct subsets. Of interest, lung CX3CR1hicDC2 subset are origin of rest of 5 subsets. In aim 1, we will test whether other lung cDC2 subsets are derived from the CX3CR1hicDC2 subset. In aim 2, we will test whether a cDC-specific CX3CR1 depletable stain (CX3CR1-DTRcDC) is responsible not only Th2 immunity but also Th17 immune responses. Successful completion of this project will provide us with a better understanding of heterogeneity and cellular dynamic lineage trajectory of lung cDC2. Moreover, our new mouse strain, cDC specific CX3CR1 depletable strain (CX3CR1-DTRcDC), will be a great asset to study cDC2-mediated diseases.

抽象的树突状细胞（DC）在弥合先天和适应性免疫方面起着基本作用。在DC亚型中，常规DC2（CDC2）在多种疾病中是关键的，包括过敏，真菌和寄生虫感染，以及癌症。然而，研究Cdc2受到小细胞数量的挑战，缺乏子集 - 特定动物模型。为了更好地了解CDC2子集的特征和作用，我们已经利用了尖端的，基于RNA的高通量转录组分析技术称为单细胞RNA- 测序（SCRNA-SEQ）。这种方法使我们能够从多样性方面更好地理解肺CDC2 和蜂窝层次结构。我们的初步数据表明，肺CDC2可以分为6个不同的子集。感兴趣的肺 CX3CR1HICDC2子集是5个子集的其余部分。在AIM 1中，我们将测试其他肺CDC2子集是否源自CX3CR1HICDC2子集。在AIM 2中，我们将测试CDC特异性的CX3CR1是否可枯竭染色（CX3CR1-DTRCDC）不仅是TH2免疫，而且还负责TH17免疫反应。该项目的成功完成将使我们更好地了解异质性和细胞肺CDC2的动态谱系轨迹。此外，我们的新老鼠菌株，cdc特异性CX3CR1可枯竭菌株（CX3CR1-DTRCDC）将是研究CDC2介导的疾病的重要资产。