Heterogeneity and cellular hierarchy of lung cDC2

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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.