F.58. Role of Plasmacytoid Dendritic Cells in the Initiation of Type I Diabetes in NOD Mice

2009 ◽  
Vol 131 ◽  
pp. S109-S110
Author(s):  
Qing Li ◽  
Hugh McDevitt
Keyword(s):  
Dendritic Cells ◽  
Type I Diabetes ◽  
Nod Mice ◽  
Plasmacytoid Dendritic Cells ◽  
Type I

scholarly journals The role of myeloid receptors on murine plasmacytoid dendritic cells in induction of type I interferon

2011 ◽  
Vol 11 (7) ◽  
pp. 794-801 ◽  
Author(s):  
Rosalind E. Seeds ◽  
Subhankar Mukhopadhyay ◽  
Ian M. Jones ◽  
Siamon Gordon ◽  
Joanna L. Miller
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
Type I

P2Y receptor signaling regulates phenotype and IFN-α secretion of human plasmacytoid dendritic cells

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 3062-3069 ◽  
Author(s):  
Amanda Shin ◽  
Tracey Toy ◽  
Simon Rothenfusser ◽  
Neil Robson ◽  
Julia Vorac ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
P2y Receptors ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
P2y Receptor ◽  
Cd40 Ligation ◽  
Kinase C ◽  
Novel Therapeutic Strategies ◽  
G Protein Coupled

Abstract Plasmacytoid dendritic cells (PDCs) play powerful regulatory roles in innate and adaptive immune responses and are a major source of type I interferon (IFN) following viral infection. During inflammation and mechanical stress, cells release nucleotides into the extracellular space where they act as signaling molecules via G protein–coupled P2Y receptors. We have previously reported on the regulation of myeloid dendritic cell (DC) function by nucleotides. Here, we report that human PDCs express several subtypes of P2Y receptors and mobilize intracellular calcium in response to nucleotide exposure. As a functional consequence, PDCs acquire a mature phenotype that is further enhanced in the context of CD40 ligation. Strikingly, nucleotides strongly inhibit IFN-α secretion induced by influenza virus or CpG-A. This effect is most pronounced for the uridine nucleotides UDP and UTP and the sugar nucleotide UDP-glucose, ligands of P2Y6, P2Y4, and P2Y14, respectively. Nucleotide-induced inhibition of IFN-α production is blocked by suramin, a P2Y receptor antagonist. Pharmacological data point toward a role of protein kinase C in the negative regulation of type I IFN. Manipulating PDC function with P2Y receptor agonists may offer novel therapeutic strategies for autoimmune diseases or cancer.

scholarly journals Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Brian Webster ◽  
Scott W Werneke ◽  
Biljana Zafirova ◽  
Sébastien This ◽  
Séverin Coléon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cell ◽  
Rna Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Virus Infections ◽  
Antiviral Responses ◽  
Infected Cells ◽  
Interferon Responses

Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections.

scholarly journals Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells

2005 ◽  
Vol 102 (39) ◽  
pp. 13974-13979 ◽  
Author(s):  
J.-P. Herbeuval ◽  
A. W. Hardy ◽  
A. Boasso ◽  
S. A. Anderson ◽  
M. J. Dolan ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Type I Ifn ◽  
Hiv 1

Role of adenosine receptors in regulating chemotaxis and cytokine production of plasmacytoid dendritic cells

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1391-1397 ◽  
Author(s):  
Max Schnurr ◽  
Tracey Toy ◽  
Amanda Shin ◽  
Gunther Hartmann ◽  
Simon Rothenfusser ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Adenosine Receptors ◽  
Plasmacytoid Dendritic Cells ◽  
Receptor Expression ◽  
Type I ◽  
Cpg Oligodeoxynucleotides ◽  
A2a Receptor ◽  
A1 Receptor ◽  
And Function

Abstract Plasmacytoid dendritic cells (PDCs) are potent regulators of immune function and the major source of type I interferon (IFN) following viral infection. PDCs are found at sites of inflammation in allergic reactions, autoimmune disorders, and cancer, but the mechanisms leading to the recruitment of PDCs to these sites remain elusive. During inflammation, adenosine is released and functions as a signaling molecule via adenosine receptors. This study analyzes adenosine receptor expression and function in human PDCs. Adenosine was found to be a potent chemotactic stimulus for immature PDCs via an A1 receptor–mediated mechanism. The migratory response toward adenosine was comparable to that seen with CXCL12 (stromal-derived factor-1α [SDF-1α), the most potent chemotactic stimulus identified thus far for immature PDCs. Upon maturation, PDCs down-regulate the A1 receptor, resulting in a loss of migratory function. In contrast, mature PDCs up-regulate the A2a receptor, which is positively coupled to adenylyl cyclase and has been implicated in the down-regulation of DC cytokine-producing capacity. We show that in mature PDCs adenosine reduces interleukin-6 (IL-6), IL-12, and IFN-α production in response to CpG oligodeoxynucleotides (ODN). These findings indicate that adenosine may play a dual role in PDC-mediated immunity by initially recruiting immature PDCs to sites of inflammation and by subsequently limiting the extent of the inflammatory response induced by mature PDCs by inhibiting their cytokine-producing capacity.

scholarly journals CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens

2004 ◽  
Vol 199 (4) ◽  
pp. 567-579 ◽  
Author(s):  
Mariolina Salio ◽  
Michael J. Palmowski ◽  
Ann Atzberger ◽  
Ian F. Hermans ◽  
Vincenzo Cerundolo
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Type I Ifn ◽  
Antiviral Responses ◽  
Specific Ctls ◽  
Antigen Presenting

Plasmacytoid dendritic cells (PDCs) are a unique leukocyte population capable of secreting high levels of type I interferon (IFN) in response to viruses and bacterial stimuli. In vitro experiments have shown that upon maturation, human and murine PDCs develop into potent immunostimulatory cells; however, their ability to prime an immune response in vivo remains to be addressed. We report that CpG-matured murine PDCs are capable of eliciting in naive mice antigen-specific CTLs against endogenous antigens as well as exogenous peptides, but not against an exogenous antigen. Type I IFN is not required for priming, as injection of CpG-matured PDCs into type I IFN receptor–deficient mice elicits functional CTL responses. Mature PDCs prime CTLs that secrete IFN-γ and protect mice from a tumor challenge. In contrast, immature PDCs are unable to prime antigen-specific CTLs. However, mice injected with immature PDCs are fully responsive to secondary antigenic challenges, suggesting that PDCs have not induced long-lasting tolerance via anergic or regulatory T cells. Our results underline the heterogeneity and plasticity of different antigen-presenting cells, and reveal an important role of mature PDCs in priming CD8 responses to endogenous antigens, in addition to their previously reported ability to modulate antiviral responses via type I IFN.

scholarly journals Physiological Role of Plasmacytoid Dendritic Cells and Their Potential Use in Cancer Immunity

2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Jorge Schettini ◽  
Pinku Mukherjee
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Antigens ◽  
Physiological Role ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Therapeutic Approaches ◽  
Adaptive Immune ◽  
Type I Ifns

Dendritic cells (DCs) play a pivotal role in the control of innate and adaptive immune responses. They are a heterogeneous cell population, where plasmacytoid dendritic cells (pDCs) are a unique subset capable of secreting high levels of type I IFNs. It has been demonstrated that pDCs can coordinate events during the course of viral infection, atopy, autoimmune diseases, and cancer. Therefore, pDC, as a main source of type I IFN, is an attractive target for therapeutic manipulations of the immune system to elicit a powerful immune response against tumor antigens in combination with other therapies. The therapeutic vaccination with antigen-pulsed DCs has shown a limited efficacy to generate an effective long-lasting immune response against tumor cells. A rational manipulation and design of vaccines which could include DC subsets outside “Langerhans cell paradigm” might allow us to improve the therapeutic approaches for cancer patients.

scholarly journals A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection

2019 ◽  
Vol 216 (9) ◽  
pp. 1974-1985 ◽  
Author(s):  
Franck J. Barrat ◽  
Lishan Su
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Plasmacytoid Dendritic Cells ◽  
Chronic Viral Infection ◽  
Type I ◽  
Main Function ◽  
Pathogenic Role ◽  
Type I Ifns ◽  
Chronic Viral Infections

Following the discovery of plasmacytoid dendritic cells (pDCs) and of their extraordinary ability to produce type I IFNs (IFN-I) in response to TLR7 and TLR9 stimulation, it is assumed that their main function is to participate in the antiviral response. There is increasing evidence suggesting that pDCs and/or IFN-I can also have a detrimental role in a number of inflammatory and autoimmune diseases, in the context of chronic viral infections and in cancers. Whether these cells should be targeted in patients and how much of their biology is connected to IFN-I production remains unclear and is discussed here.

scholarly journals Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women

2021 ◽  
Vol 12 ◽  
Author(s):  
Jean-Charles Guéry
Keyword(s):  
Dendritic Cells ◽  
Hiv Infection ◽  
X Chromosome ◽  
Type I Interferon ◽  
Acute Infection ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Hiv 1 ◽  
Tlr7 Stimulation

Plasmacytoid dendritic cells (pDCs) produce type I interferon (IFN-I) during HIV-1 infection in response to TLR7 stimulation. However, IFN-I-signaling has been shown to play opposite effects in HIV-1 and SIV infection. TLR7-driven type I interferon production in pDCs is higher in women than in men due to the cell-intrinsic actions of estrogen and X-chromosome complement. Indeed, TLR7 is encoded on the X-chromosome, and the TLR7 gene escapes the X-chromosome inactivation in immune cells of women which express significantly higher levels of TLR7 protein than male cells. Following HIV infection, women have a lower viremia during acute infection and exhibit stronger antiviral responses than men, which has been attributed to the increased capacity of female pDCs to produce IFN-α upon TLR7-stimulation. However, a deleterious functional impact of an excessive TLR7 response on acute viremia in women has been recently revealed by the analysis of the frequent rs179008 c.32A>T SNP of TLR7. This SNP was identified as a sex-specific protein abundance quantitative trait locus (pQTL) causing a difference in the TLR7 protein dosage and effector function in females only. T allele expression was associated with a lower TLR7 protein synthesis, blunted production of IFN-α by pDCs upon TLR7 stimulation, and an unexpectedly lower viral load during primary HIV-1 infection in women. In the present review, the author will revisit the role of TLR7-driven pDC innate function in the context of HIV-1 infection to discuss at what stage of primary HIV-1 infection the TLR7 rs179008 T allele is likely to be protective in women.

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