Plasmacytoid dendritic cells in dermatology

Abstract

Plasmacytoid dendritic cells are part of the dendritic cells family and are a relevant link between innate and adaptive immunity. They are the most potent producers of type 1 interferon, generating antiviral response, stimulating macrophages and dendritic cells and inducing activation and migration of natural killer cells. Plasmacytoid dendritic cells also exert a role as antigen-presenting cells, promote T-lymphocyte responses, immunoregulation, plasma cells differentiation and antibody secretion. Even though plasmacytoid dendritic cells are not usually present in normal skin, their presence is detected in healing processes, viral infections, and inflammatory, autoimmune, and neoplastic diseases. In recent years, the presence of plasmacytoid dendritic cells in several dermatological diseases has been described, enhancing their potential role in the pathogenesis of such conditions. Future studies on the role of plasmacytoid dendritic cells in dermatology may lead to new therapeutic targets.

The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum

“…Plasmacytoid dendritic cells are able to produce large amounts of IFN-I and, when activated, migrate from the blood to the affected tissues ( 12 ). Indeed, the cutaneous infiltration of these cells is a histological hallmark in inflammatory and autoimmune diseases affecting the skin, upon which they imprint an IFN-I signature ( 15 – 18 ). In humans, pDCs express a rather specific set of cell surface markers such as the blood dendritic cell antigen 2 (BDCA-2) and BDCA-4, along with a high expression of CD123, the alpha subunit of the IL-3 receptor ( 10 ).…”

“…In this study, all CD123 + cells found in the lesions were also shown to express BDCA2 and/or BDCA4, specific markers of these cells. The above authors reported higher concentrations of pDCs in the skin lesions of Type I reactional (RR) patients compared to non-reactional ones, inferring that pDCs may also play a role in this type of reactional episode, probably through the capacity of these cells to enhance both innate and adaptive immune responses via numerous mechanisms ( 18 ).…”

“…The present results also suggest the involvement of ENL pDCs in type I IFN production, the major source of these cytokines in the body. The pDC/IFN-I pathway has been specifically implicated in the pathogenesis of skin manifestations in chronic inflammatory/autoimmune diseases in which an enrichment of pDCs in the inflammatory infiltrate in association with an IFN-I signature has been demonstrated ( 9 , 18 ). Of note, a recent therapeutic approach in the treatment of cutaneous lupus targeting pDCs has shown promising results ( 80 ), which may prove useful in treating ENL as well.…”

“…Increasing evidence also points to plasmacytoid dendritic cells (pDCs) as the major source of IFN-α/β in these diseases via the recognition of extracellular self-nucleic acids such as nucleic acid-immune complexes and extracellular neutrophil traps (NETs) by way of the toll-like receptors 7 (TLR7) and 9 (TLR9; 5 , 9 , 10 , 14 ). The pathogenic role of pDCs-derived IFN-I has been especially emphasized in inflammatory diseases with cutaneous manifestations during which these cells accumulate in the skin lesions ( 15 – 18 ).…”

Mice Plasmacytoid Dendritic Cells Were Activated by Lipopolysaccharides Through Toll-Like Receptor 4/Myeloid Differentiation Factor 2

“…However, when compared to cDCs, due to the low expression of MHC and costimulatory molecules, pDCs are not efficient at presenting antigens and mediating T cell activation. They become potent APCs upon proper stimulation with TLR ligands, such as the TLR9 agonist CpG and TLR7 agonist imiquimod ( 36 , 37 ). In addition, it has been demonstrated that human pDCs express TLR1/2.…”