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TRANSITIONAL DENDRITIC CELLS ARE DISTINCT FROM CONVENTIONAL DC2 PRECURSORS AND MEDIATE PRO-INFLAMMATORY ANTIVIRAL RESPONSES

ABSTRACT: TRANSITIONAL DENDRITIC CELLS ARE DISTINCT FROM CONVENTIONAL DC2 PRECURSORS AND MEDIATE PRO-INFLAMMATORY ANTIVIRAL RESPONSES

PROVIDER: PRJNA815954 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18322374.fastq.gz	Fastqsanger.gz
	SRR18322375.fastq.gz	Fastqsanger.gz
	SRR18322376.fastq.gz	Fastqsanger.gz
	SRR18322377.fastq.gz	Fastqsanger.gz

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TRANSITIONAL DENDRITIC CELLS ARE DISTINCT FROM CONVENTIONAL DC2 PRECURSORS AND MEDIATE PRO-INFLAMMATORY ANTIVIRAL RESPONSES

Project description:High-dimensional approaches revealed emerging heterogeneity within dendritic cells (DC), including a population of transitional DC (tDC) present in mouse and human. However, tDC origin and relationship to other DC subsets are not fully understood. Here, we show that tDC are distinct from other well-characterized DC and conventional DC precursors (pre-cDC). We demonstrate that tDC originate from bone marrow progenitors shared with plasmacytoid DC (pDC). In the periphery, tDC contribute to the pool of ESAM+ type 2 DC (DC2), and these DC2 harbor pDC-related developmental features. Different from pre-cDC, tDC have lower turnover, capture antigen, respond to stimuli, and activate antigen-specific naïve T cells, all characteristics of differentiated DC. Different from pDC, viral sensing by tDC results in IL-1b secretion and fatal immune pathology in a murine coronavirus model. Our findings suggest that tDC are a distinct pDC-related subset with a DC2 differentiation potential and unique pro-inflammatory function during viral infections.

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Project description:By combining single cell transcriptomics and proteomics approaches, with lineage tracing and adoptive transfer experiments, we next demonstrate that tDC originate from a bone marrow precursor shared with plasmacytoid DCs (pDCs). Using new lineage tracing mouse models, we evaluated tDC plasticity and reveal their acquisition of Esamhi conventional DC type 2 (cDC2) features. Finally, we present tDC capacity to quickly response to stimulation and potently activate antigen-specific naïve T cells, demonstrating that these cells harbor functions of differentiated DCs. Our findings clarify tDC nature and reveal these cells as a unique lineage of DCs related developmentally to pDCs.

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