Integrated Cross-Species Analysis Identifies a Conserved Transitional Dendritic Cell Population

Abstract

Summary: Plasmacytoid dendritic cells (pDCs) are sensor cells with diverse immune functions, from type I interferon (IFN-I) production to antigen presentation, T cell activation, and tolerance. Regulation of these functions remains poorly understood but could be mediated by functionally specialized pDC subpopulations. We address pDC diversity using a high-dimensional single-cell approach: mass cytometry (CyTOF). Our analysis uncovers a murine pDC-like population that specializes in antigen presentation with limited capacity for IFN-I production. Using a multifaceted cross-species comparison, we show that this pDC-like population is the definitive murine equivalent of the recently described human AXL+ DCs, which we unify under the name transitional DCs (tDCs) given their continuum of pDC and cDC2 characteristics. tDCs share developmental traits with pDCs, as well as recruitment dynamics during viral infection. Altogether, we provide a framework for deciphering the function of pDCs and tDCs during diseases, which has the potential to open new avenues for therapeutic design. : Dendritic cells (DCs) are unique therapeutic targets given their capacity to modulate immune responses. Yet complete alignment of the DC network between species is lacking. Using a multi-dimensional approach, Leylek et al. identify the mouse homolog of human AXL+ DCs, named transitional DCs (tDCs), and reveal their similarities with pDCs. Keywords: plasmacytoid dendritic cells, transitional dendritic cells, AXL+ dendritic cells, noncanonical dendritic cells, viral infection, mouse, human, CyTOF, ASDC, pre-DCs