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Review
. 2019 Jan 15;50(1):37-50.
doi: 10.1016/j.immuni.2018.12.027.

Plasmacytoid Dendritic Cells: Development, Regulation, and Function

Affiliations
Review

Plasmacytoid Dendritic Cells: Development, Regulation, and Function

Boris Reizis. Immunity. .

Abstract

Plasmacytoid dendritic cells (pDCs) are a unique sentinel cell type that can detect pathogen-derived nucleic acids and respond with rapid and massive production of type I interferon. This review summarizes our current understanding of pDC biology, including transcriptional regulation, heterogeneity, role in antiviral immune responses, and involvement in immune pathology, particularly in autoimmune diseases, immunodeficiency, and cancer. We also highlight the remaining gaps in our knowledge and important questions for the field, such as the molecular basis of unique interferon-producing capacity of pDCs. A better understanding of cell type-specific positive and negative control of pDC function should pave the way for translational applications focused on this immune cell type.

Keywords: Plasmacytoid dendritic cells (pDCs) are innate immune sentinels that play important roles in immunity to infection and autoimmunity. This review by Boris Reizis highlights recent progress and emerging areas of interest in pDC biology as well as translational applications.

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Figures

Figure 1
Figure 1
Transcriptional Control of pDC Lineage Transcription factors with enriched expression in pDCs, cDCs, or all DCs are shown in red, blue, or violet, respectively. (A) Transcription factors that regulate pDC specification in the bone marrow. Lineage splits leading to alternative cell fates including cDC1s and non-canonical DCs are highlighted. TCF4L denotes the pDC-specific long isoform of TCF4. (B) Transcription factors that regulate the differentiation of committed pDCs in the bone marrow and pDC functionality in the periphery.
Figure 2
Figure 2
The Proposed Spectrum of Dendritic Cell Subsets Shown on this hypothetical scheme are canonical pDCs and cDCs (including cDC1 and cDC2) and the intermediate “non-canonical” populations including non-canonical pDCs (nc-pDC) and cDCs (nc-cDC). Shown are functional properties including the IFN-I production capacity and antigen presentation capacity in the steady state, expression of key transcription factors, and surface markers in the human (Alcántara-Hernández et al., 2017, Villani et al., 2017) and mouse (Bar-On et al., 2010, Lau et al., 2016, Dekker et al., 2018). Italicized genes and markers denote expression based on reported transcript levels.
Figure 3
Figure 3
The Mechanism of pDC Activation (A) Activation by TLR ligands or viruses that do not infect pDCs. Shown is the traditional “cell-intrinsic” model and the emerging “cooperative” model that highlights homotypic interaction between pDCs and directional signaling and IFN secretion. (B) Activation by viruses that infect and replicate in pDCs. Shown is the “cell-intrinsic” model based on autophagy-mediated TLR signaling, and the proposed “cooperative” model whereby virus replication and TLR signaling occur in different cells, and TLR ligands are transferred via exosomes or viral particles. An infected cell is highlighted in dark gray. (C) Activation by viruses that infect cells other than pDCs. TLR ligands are transferred from infected cells (highlighted in dark gray) to pDCs during polarized contact via exosomes or viral particles.

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