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

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. Examination of immune cells in murine bone marrow and spleen. Cells were CD135 enriched and sorted for live cells. Cells were barcoded, pooled and run on 2 lanes. Sorted splenocytes were mixed 1:1 from 2 gates: CD3-/CD19-/NK1.1-/Ly6G- and CD3-/CD19-/NK1.1-/Ly6G-/Xcr1-/CD11blo to enrich for tDC. BM cells were gated as CD3-/CD19-/NK1.1-/Ly6G-. After sort, cells were counted and resuspended at a concentration of 600 cells per uL. Cells suspensions were processed for 10X Genomics.