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      Plasmacytoid Dendritic Cells: Development, Regulation, and Function

      review-article
      1 ,
      Immunity
      Elsevier Inc.

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          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.

          Abstract

          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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          Most cited references153

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          The nature of the principal type 1 interferon-producing cells in human blood.

          Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
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            Plasmacytoid dendritic cells in immunity.

            Human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts of type I interferons in response to viruses, the so-called natural interferon-producing cells. As a result, intensive investigation is now focused on the potential functions of plasmacytoid dendritic cells in both innate and adaptive immunity. Here we review recent progress on the characterization of plasmacytoid dendritic cell origin, development, migration and function in immunity and tolerance, as well as their effect on human diseases.
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              Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon.

              We have identified two cell subsets in human blood based on the lack of lineage markers (lin-) and the differential expression of immunoglobulin-like transcript receptor 1 (ILT1) and ILT3. One subset (lin-/ILT3+/ILT1+) is related to myeloid dendritic cells. The other subset (lin-/ILT3+/ILT1+) corresponds to 'plasmacytoid monocytes'. These cells are found in inflamed lymph nodes in and around the high endothelial venules. They express CD62L and CXCR3, and produce extremely large amounts of type I interferon after stimulation with influenza virus or CD40L. These results, with the distinct cell phenotype, indicate that plasmacytoid monocytes represent a specialized cell lineage that enters inflamed lymph nodes at high endothelial venules, where it produces type I interferon. Plasmacytoid monocytes may protect other cells from viral infections and promote survival of antigen-activated T cells.
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                Author and article information

                Contributors
                Journal
                Immunity
                Immunity
                Immunity
                Elsevier Inc.
                1074-7613
                1097-4180
                15 January 2019
                15 January 2019
                15 January 2019
                : 50
                : 1
                : 37-50
                Affiliations
                [1 ]Department of Pathology and Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
                Author notes
                []Corresponding author boris.reizis@ 123456nyumc.org
                Article
                S1074-7613(18)30575-2
                10.1016/j.immuni.2018.12.027
                6342491
                30650380
                cf4cc3b2-e064-4fc9-8900-2cb9f3a8ea7b
                © 2018 Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Immunology
                Immunology

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