Unraveling dendritic-cell diversity in blood of pigs: welcome tDC and DC3

Dendritic cells (DC) are professional antigen presenting cells playing a major role in orchestrating adaptative immune responses. To adapt to various immune challenges, such as different classes of pathogens, specialized subsets of DC have evolved across species. To date, DC are classified as conventional DC (cDC1, cDC2) and plasmacytoid DC (pDC), with the more recent addition of DC3 and transitional DC (tDC) that were discovered in human and mouse thanks to high-dimensional phenotyping and single-cell sequencing technologies. Here, by combining flow cytometry and RNA-seq on the bulk- and single-cell level, we identified the porcine equivalent of tDC in blood as CD14-CADM1-CD172a+CD4-cells expressing both Flt3 and CD123 (IL-3RA). This new subset forms a well-defined cluster when mapped onto scRNA-seq data of enriched DC and shares transcriptomic features and abundance with porcine blood cDC2 and pDC. Moreover, we describe putative porcine DC3 as transcriptionally overlapping cells in-between cDC2 and monocytes. With the core functions of tDC and DC3 remaining to be elucidated, our datasets provide a valuable resource for cross-species research on DC heterogeneity in various lymphoid and non-lymphoid tissues.