Faculty Opinions recommendation of Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons.

2011 ◽  
Author(s):  
Caetano Reis e Sousa ◽  
Barbara Schraml
Keyword(s):  
Wound Healing ◽  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Skin Injury ◽  
Promote Wound Healing

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor α signaling

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 454-464 ◽  
Author(s):  
Cyril Seillet ◽  
Sophie Laffont ◽  
Florence Trémollières ◽  
Nelly Rouquié ◽  
Claude Ribot ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Genetic Ablation ◽  
17Β Estradiol ◽  
Female Host

Plasmacytoid dendritic cells (pDCs) produce large amounts of type I interferons (IFN-α/β) in response to viral or endogenous nucleic acids through activation of their endosomal Toll-like receptors (TLR-7 and TLR-9). Enhanced TLR-7–mediated IFN-α production by pDCs in women, compared with men, has been reported, but whether sex hormones, such as estrogens, are involved in this sex-based difference is unknown. Here we show, in humanized mice, that the TLR-7–mediated response of human pDCs is increased in female host mice relative to male. In a clinical trial, we establish that treatment of postmenopausal women with 17β-estradiol markedly enhances TLR-7– and TLR-9–dependent production of IFN-α by pDCs stimulated by synthetic ligands or by nucleic acid-containing immune complexes. In mice, we found exogenous and endogenous estrogens to promote the TLR-mediated cytokine secretion by pDCs through hematopoietic expression of estrogen receptor (ER) α. Genetic ablation of ERα gene in the DC lineage abrogated the enhancing effect of 17β-estradiol on their TLR-mediated production of IFN-α, showing that estrogens directly target pDCs in vivo. Our results uncover a previously unappreciated role for estrogens in regulating the innate functions of pDCs, which may account for sex-based differences in autoimmune and infectious diseases.

scholarly journals Sources of Type I Interferons in Infectious Immunity: Plasmacytoid Dendritic Cells Not Always in the Driver's Seat

2019 ◽  
Vol 10 ◽  
Author(s):  
Shafaqat Ali ◽  
Ritu Mann-Nüttel ◽  
Anja Schulze ◽  
Lisa Richter ◽  
Judith Alferink ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Infectious Immunity

scholarly journals HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells

2019 ◽  
Author(s):  
Qi Wang ◽  
Li-Chung Tsao ◽  
Lei Lv ◽  
Yanping Xu ◽  
Liang Cheng ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Constitutive Expression ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Hiv 1

AbstractPlasmacytoid dendritic cells (pDCs) are the major source of type I interferons (IFN-I) in rapid response to viral infections, with constitutive expression of interferon regulatory factor 7 (IRF7). HIV-1 expresses several accessory proteins to counteract specific IFN-induced host restriction factors. As one abundant virion-associated protein, HIV-1 Vpr remains enigmatic in enhancing HIV-1 infection via unclear mechanisms. Here we report that Vpr impaired IFN-I induction in pDCs to enhance HIV-1 replication in CD4+ T cells. Blockade of IFN-I signaling abrogated the effect of Vpr on HIV-1 replication. Virion-associated Vpr suppressed IFN-I induction in pDC by TLR7 agonists. Modulation of IFN-I induction by Vpr was genetically dependent on its activity of TET2 degradation. We further demonstrate that Vpr-mediated TET2 degradation reduced expression of IRF7 in pDCs. Finally, degradation of TET2 in pDCs by Vpr reduced the demethylation level of the IRF7 promoter via CXXC5-dependent recruitment. We conclude that HIV-1 Vpr functions to promote HIV-1 replication by suppressing TET2-dependent IRF7 expression and IFN-I induction in pDCs. The Vpr-TET2-IRF7 axis provides a novel therapeutic target to control HIV-1 infection.

scholarly journals The transcription factor reservoir and chromatin landscape in activated plasmacytoid dendritic cells

2021 ◽  
Author(s):  
Ritu Mann-Nüttel ◽  
Shafaqat Ali ◽  
Patrick Petzsch ◽  
Karl Köhrer ◽  
Judith Alferink ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Time Course ◽  
Target Genes ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
A Cell ◽  
Direct Binding ◽  
Time Course Study

Transcription factors (TFs) control gene expression by direct binding to regulatory regions of target genes but also by impacting chromatin landscapes and thereby modulating DNA accessibility for other TFs. To date, the global TF reservoir in plasmacytoid dendritic cells (pDCs), a cell type with the unique capacity to produce unmatched amounts of type I interferons, has not been fully characterized. To fill this gap, we have performed a comprehensive analysis in naïve and TLR9-activated pDCs in a time course study covering early timepoints after stimulation (2h, 6h, 12h) integrating gene expression (RNA-Seq), chromatin landscape (ATAC-Seq) and Gene Ontology studies. We found that 70% of all described TFs are expressed in pDCs for at least one stimulation time point and that activation predominantly "turned on" the chromatin regions associated with TF genes. We hereby define the complete set of TLR9-regulated TFs in pDCs. Further, this study identifies the AP-1 family of TFs as potentially important but so far less well characterized regulators of pDC function.

Differential expression of type I interferon genes in plasmacytoid dendritic cells from HIV-infected patientss

2007 ◽  
Vol 30 (4) ◽  
pp. 84
Author(s):  
Martin D. Hyrcza ◽  
Sandy S. Der ◽  
Mario Ostrowski
Keyword(s):  
Dendritic Cells ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Cpg Dna ◽  
Ifn Alpha ◽  
Hiv Virus ◽  
Peripheral T Cells

Background: Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFN). Human genome contains thirteen IFN alpha genes and one IFN beta gene. Research in mice suggests that different IFNs are induced by different stimuli, but whether this is true in human cells is unknown. Patients with HIV-1 infection show chronic interferon response in peripheral T cells, which caused us to analyze the induction of the IFN alpha genes in their dendritic cells. Methods: Uninfected, acutely infected and long-term non-progressive donors were leukopheresed, following which pDCs were isolated by negative depletion. The dendritic cells were then treated for with one of the following: influenza virus, sendai virus, HIV virus, CpG DNA, imiquimod, or media alone, and the cells’ RNA was analysed by real time qPCR for changes in the RNA levels of four IFN alpha genes: α1, α2, α7, α8, as well as IFN beta. Results: Final results were not available at the time of abstract deposition.

scholarly journals TRIM8 is required for virus-induced IFN response in human plasmacytoid dendritic cells

2019 ◽  
Vol 5 (11) ◽  
pp. eaax3511 ◽  
Author(s):  
Ghizlane Maarifi ◽  
Nikaïa Smith ◽  
Sarah Maillet ◽  
Olivier Moncorgé ◽  
Célia Chamontin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Prolyl Isomerase ◽  
Independent Manner ◽  
Peptidyl Prolyl Isomerase ◽  
The Stability ◽  
Antiviral Innate Immunity ◽  
Trim Proteins

Plasmacytoid dendritic cells (pDCs) play a crucial role in antiviral innate immunity through their unique capacity to produce large amounts of type I interferons (IFNs) upon viral detection. Tripartite motif (TRIM) proteins have recently come forth as important modulators of innate signaling, but their involvement in pDCs has not been investigated. Here, we performed a rationally streamlined small interfering RNA (siRNA)–based screen of TRIM proteins in human primary pDCs to identify those that are critical for the IFN response. Among candidate hits, TRIM8 emerged as an essential regulator of IFN regulatory factor 7 (IRF7) function. Mechanistically, TRIM8 protects phosphorylated IRF7 (pIRF7) from proteasomal degradation in an E3 ubiquitin ligase–independent manner by preventing its recognition by the peptidyl-prolyl isomerase Pin1. Our findings uncover a previously unknown regulatory mechanism of type I IFN production in pDCs by which TRIM8 and Pin1 oppositely regulate the stability of pIRF7.

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