Heterogeneity and cellular hierarchy of lung cDC2

肺 cDC2 的异质性和细胞层次

• 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
• 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

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.

摘要 树突状细胞（Dendritic cells，DCs）在天然免疫和适应性免疫中起重要作用。在DC亚型中， 常规DC 2（cDC 2）在多种疾病中起关键作用，包括过敏、真菌和寄生虫感染， 癌然而，研究cDC 2受到了小细胞数量和缺乏亚群的挑战。 特定动物模型。为了更好地理解cDC 2亚群的特征和作用，我们利用了 尖端的，基于RNA的高通量转录组学分析技术，称为单细胞RNA- 测序（scRNA-seq）。这种方法使我们能够更好地了解肺cDC 2的多样性， 和细胞层次。 我们的初步数据表明，肺cDC 2可以分为6个不同的子集。感兴趣，龙哥 CX 3CR 1hicDC 2亚群是其余5个亚群的起源。在目标1中，我们将测试其他肺cDC 2亚群是否 来自CX 3CR 1hicDC 2亚群。在目标2中，我们将测试是否存在cDC特异性CX 3CR 1可耗竭性。 染色剂（CX 3CR 1-DTRcDC）不仅负责Th 2免疫，而且负责Th 17免疫应答。 这个项目的成功完成将使我们更好地了解异质性和细胞 肺cDC 2的动态谱系轨迹。此外，我们的新小鼠品系，cDC特异性CX 3CR 1耗竭 菌株CX 3CR 1-DTRcDC，将是研究cDC 2介导疾病的重要资产。