The versatile plasmacytoid dendritic cell: Function, heterogeneity, and plasticity.
International review of cell and molecular biology
2019; 349: 177–211
Since their identification as the natural interferon-producing cell two decades ago, plasmacytoid dendritic cells (pDCs) have been attributed diverse functions in the immune response. Their most well characterized function is innate, i.e., their rapid and robust production of type-I interferon (IFN-I) in response to viruses. However, pDCs have also been implicated in antigen presentation, activation of adaptive immune responses and immunoregulation. The mechanisms by which pDCs enact these diverse functions are poorly understood. One central debate is whether these functions are carried out by different pDC subpopulations or by plasticity in the pDC compartment. This chapter summarizes the latest reports regarding pDC function, heterogeneity, cell conversion and environmentally influenced plasticity, as well as the role of pDCs in infection, autoimmunity and cancer.
View details for DOI 10.1016/bs.ircmb.2019.10.002
View details for PubMedID 31759431
Integrated Cross-Species Analysis Identifies a Conserved Transitional Dendritic Cell Population.
2019; 29 (11): 3736–50.e8
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.
View details for DOI 10.1016/j.celrep.2019.11.042
View details for PubMedID 31825848
High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization.
Given the limited efficacy of clinical approaches that rely on ex vivo generated dendritic cells (DCs), it is imperative to design strategies that harness specialized DC subsets in situ. This requires delineating the expression of surface markers by DC subsets among individuals and tissues. Here, we performed a multiparametric phenotypic characterization and unbiased analysis of human DC subsets in blood, tonsil, spleen, and skin. We uncovered previously unreported phenotypic heterogeneity of human cDC2s among individuals, including variable expression of functional receptors such as CD172a. We found marked differences in DC subsets localized in blood and lymphoid tissues versus skin, and a striking absence of the newly discovered Axl+ DCs in the skin. Finally, we evaluated the capacity of anti-receptor monoclonal antibodies to deliver vaccine components to skin DC subsets. These results offer a promising path for developing DC subset-specific immunotherapies that cannot be provided by transcriptomic analysis alone.
View details for PubMedID 29221729