Heterogeneity and cellular hierarchy of lung cDC2

摘要 树突状细胞(DC)在连接先天免疫和获得性免疫中起着重要作用。在DC亚型中， 传统的DC2(CDC2)在包括过敏、真菌和寄生虫感染在内的多种疾病中起关键作用。 癌症。然而，cDC2的研究受到了细胞数量较少和缺乏子集的挑战。 特定的动物模型。为了更好地理解cDC2子集的特征和作用，我们使用了 尖端的，基于RNA的高通量转录图谱技术，称为单细胞RNA- 测序(scRNA-seq)。这种方法使我们能够从多样性的角度更好地了解肺cdc2。 和蜂窝层次结构。 我们的初步数据表明，肺CDC2可分为6个不同的亚集。感兴趣的，肺 CX3CR1hicDC2子集是其余5个子集的起源。在目标1中，我们将测试其他肺cDC2亚群 是从CX3CR1hicDC2子集派生的。在目标2中，我们将测试CDC特定的CX3CR1是否可耗尽 菌株(CX3CR1-DTRcDC)不仅负责Th2免疫，而且还负责Th17免疫应答。 这个项目的成功完成将使我们更好地了解异构性和细胞 肺cDC2的动态谱系轨迹。此外，我们的新小鼠品系CDC特异性CX3CR1可耗尽 CX3CR1-DTRcDC，将是研究cDC2介导性疾病的宝贵财富。

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.