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      Disease-Associated Plasmacytoid Dendritic Cells

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          Abstract

          Plasmacytoid dendritic cells (pDCs), also called natural interferon (IFN)-producing cells, represent a specialized cell type within the innate immune system. pDCs are specialized in sensing viral RNA and DNA by toll-like receptor-7 and -9 and have the ability to rapidly produce massive amounts of type 1 IFNs upon viral encounter. After producing type 1 IFNs, pDCs differentiate into professional antigen-presenting cells, which are capable of stimulating T cells of the adaptive immune system. Chronic activation of human pDCs by self-DNA or mitochondrial DNA contributes to the pathogenesis of systemic lupus erythematosis and IFN-related autoimmune diseases. Under steady-state conditions, pDCs play an important role in immune tolerance. In many types of human cancers, recruitment of pDCs to the tumor microenvironment contributes to the induction of immune tolerance. Here, we provide a systemic review of recent progress in studies on the role of pDCs in human diseases, including cancers and autoimmune/inflammatory diseases.

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          Most cited references119

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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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            Mapping the human DC lineage through the integration of high-dimensional techniques

            Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here, we combine two high-dimensional technologies—single-cell mRNA sequencing and cytometry by time-of-flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed subpopulations, including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.
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              Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency.

              Severe influenza disease strikes otherwise healthy children and remains unexplained. We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication. These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity. Copyright © 2015, American Association for the Advancement of Science.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                16 October 2017
                2017
                : 8
                : 1268
                Affiliations
                [1] 1Institute of Translational Medicine, The First Hospital, Jilin University , Changchun, China
                [2] 2Sanofi Research and Development , Cambridge, MA, United States
                Author notes

                Edited by: John Isaacs, Newcastle University, United Kingdom

                Reviewed by: Lennart T. Mars, Institut national de la santé et de la recherche médicale, France; Albert Rizvanov, Kazan Federal University, Russia; Muzlifah Aisha Haniffa, Newcastle University, United Kingdom

                *Correspondence: Jingtao Chen, jtchen@ 123456jlu.edu.cn

                These authors have contributed equally to this work.

                Specialty section: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2017.01268
                5649186
                29085361
                4ee9c758-6518-4211-af9b-681fa9e0b87b
                Copyright © 2017 Li, Wu, Zhu, Liu and Chen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 November 2016
                : 22 September 2017
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 140, Pages: 12, Words: 10295
                Funding
                Funded by: Key Scientific Project of Jilin Province
                Award ID: 20160520141JH
                Funded by: Youth Development Fund of the First Hospital of Jilin University
                Award ID: JDYY52015031
                Funded by: Platform Construction Project of Development and Reform Commission of Jilin Province
                Award ID: 2014N147
                Categories
                Immunology
                Review

                Immunology
                plasmacytoid dendritic cells,dysregulation,malignancy,autoimmune disease,tumor microenvironment

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