scholarly journals Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells

2013 ◽  
Vol 210 (11) ◽  
pp. 2151-2159 ◽  
Author(s):  
Catherine M. Sawai ◽  
Vanja Sisirak ◽  
Hiyaa S. Ghosh ◽  
Esther Z. Hou ◽  
Michele Ceribelli ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Transcription Factor ◽  
Chemokine Receptors ◽  
Bone Development ◽  
System Development ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Differentiated Cells ◽  
Immune System Development ◽  
And Migration

Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical DCs (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. pDCs in Runx2-deficient mice developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes, including the chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the cell surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.

scholarly journals Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow

Blood ◽  
2005 ◽  
Vol 105 (11) ◽  
pp. 4407-4415 ◽  
Author(s):  
Rosana Pelayo ◽  
Jun Hirose ◽  
Jiaxue Huang ◽  
Karla P. Garrett ◽  
Alessio Delogu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Transcription Factor ◽  
Fluorescent Protein ◽  
Early Stage ◽  
Consensus Sequence ◽  
Plasmacytoid Dendritic Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Interferon Α ◽  
Type I

Abstract Plasmacytoid dendritic cells (pDCs) competent to make type I interferon were rigorously defined as a Ly-6C+ and CD11cLo subset of the B220+CD19- CD43+CD24Lo bone marrow (BM) Fraction A. Otherwise similar Ly6C- cells expressed the natural killer (NK) markers DX5 and NK1.1. pDCs represented a stable, discrete, and long-lived population. Stem cells and early lymphoid progenitors (ELPs), but not prolymphocytes, were effective precursors of pDCs, and their differentiation was blocked by ligation of Notch receptors. Furthermore, pDCs were present in the BM of RAG1-/-, CD127/IL-7Ra-/-, and Pax5-/- mice. pDCs in RAG1/GFP knock-in mice could be subdivided, and immunoglobulin DH-JH rearrangements, as well as transcripts for the B-lineage–related genes Pax5, mb1/CD79a, ebf, and Bcl11a, were identified only in the green fluorescent protein–positive (GFP+) pDC1 subset. All pDCs expressed terminal deoxynucleotidyl transferase (TdT), the ETS transcription factor Spi-B, the nuclear factor-κB transcription factor RelB, toll-like receptor 9 (TLR9), and interferon consensus sequence binding protein (ICSBP)/interferon regulatory factor 8 (IRF-8) transcripts; lacked CD16 and granulocyte colony-stimulating factor receptor (G-CSFR); and were uniformly interleukin-7 receptor α (IL-7Rα-) AA4.1Lo, CD27-, Flk-2Lo, c-Kit-, DX-5-, and CD11b-, while CD4 and CD8α were variable. GFP+ pDC1 subset was less potent than GFP- pDC2s in T allostimulation and production of tumor necrosis factor α (TNFα), interferon α (IFNα), and interleukin-6 (IL-6), while only pDC2s made IFNγ and IL-12 p70. Thus, 2 functionally specialized subsets of pDCs arise in bone marrow from progenitors that diverge from B, T, and NK lineages at an early stage.

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.

scholarly journals Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells

2021 ◽  
Vol 6 (58) ◽  
pp. eabc7302
Author(s):  
Tae Jin Yun ◽  
Suzu Igarashi ◽  
Haoquan Zhao ◽  
Oriana A. Perez ◽  
Marcus R. Pereira ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Virus Detection ◽  
Plasmacytoid Dendritic Cells ◽  
Lung Epithelial Cells ◽  
Live Cells ◽  
Type I ◽  
Antiviral Immune Response ◽  
Lung Epithelial ◽  
Functional Consequences ◽  
Infected Cells

Plasmacytoid dendritic cells (pDCs) can rapidly produce interferons and other soluble factors in response to extracellular viruses or virus mimics such as CpG-containing DNA. pDCs can also recognize live cells infected with certain RNA viruses, but the relevance and functional consequences of such recognition remain unclear. We studied the response of primary DCs to the prototypical persistent DNA virus, human cytomegalovirus (CMV). Human pDCs produced high amounts of type I interferon (IFN-I) when incubated with live CMV-infected fibroblasts but not with free CMV; the response involved integrin-mediated adhesion, transfer of DNA-containing virions to pDCs, and the recognition of DNA through TLR9. Compared with transient polyfunctional responses to CpG or free influenza virus, pDC response to CMV-infected cells was long-lasting, dominated by the production of IFN-I and IFN-III, and lacked diversification into functionally distinct populations. Similarly, pDC activation by influenza-infected lung epithelial cells was highly efficient, prolonged, and dominated by interferon production. Prolonged pDC activation by CMV-infected cells facilitated the activation of natural killer cells critical for CMV control. Last, patients with CMV viremia harbored phenotypically activated pDCs and increased circulating IFN-I and IFN-III. Thus, recognition of live infected cells is a mechanism of virus detection by pDCs that elicits a unique antiviral immune response.

scholarly journals Lymphocytoid Choriomeningitis Virus Activates Plasmacytoid Dendritic Cells and Induces a Cytotoxic T-Cell Response via MyD88

2007 ◽  
Vol 82 (1) ◽  
pp. 196-206 ◽  
Author(s):  
Andreas Jung ◽  
Hiroki Kato ◽  
Yutaro Kumagai ◽  
Himanshu Kumar ◽  
Taro Kawai ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Intracellular Signaling ◽  
Plasmacytoid Dendritic Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Type I ◽  
Ctl Response ◽  
Type I Ifns ◽  
Lcmv Infection

ABSTRACTToll-like receptors (TLRs) and retinoic acid-inducible gene I-like helicases (RLHs) are two major machineries recognizing RNA virus infection of innate immune cells. Intracellular signaling for TLRs and RLHs is mediated by their cytoplasmic adaptors, i.e., MyD88 or TRIF and IPS-1, respectively. In the present study, we investigated the contributions of TLRs and RLHs to the cytotoxic T-lymphocyte (CTL) response by using lymphocytoid choriomeningitis virus (LCMV) as a model virus. The generation of virus-specific cytotoxic T lymphocytes was critically dependent on MyD88 but not on IPS-1. Type I interferons (IFNs) are known to be important for the development of the CTL response to LCMV infection. Serum levels of type I IFNs and proinflammatory cytokines were mainly dependent on the presence of MyD88, although IPS-1−/−mice showed a decrease in IFN-α levels but not in IFN-β and proinflammatory cytokine levels. Analysis ofIfna6+/GFPreporter mice revealed that plasmacytoid dendritic cells (DCs) are the major source of IFN-α in LCMV infection. MyD88−/−mice were highly susceptible to LCMV infection in vivo. These results suggest that recognition of LCMV by plasmacytoid DCs via TLRs is responsible for the production of type I IFNs in vivo. Furthermore, the activation of a MyD88-dependent innate mechanism induces a CTL response, which eventually leads to virus elimination.

scholarly journals STING-Licensed Macrophages Prime Type I IFN Production by Plasmacytoid Dendritic Cells in the Bone Marrow during Severe Plasmodium yoelii Malaria

2016 ◽  
Vol 12 (10) ◽  
pp. e1005975 ◽  
Author(s):  
Emily Spaulding ◽  
David Fooksman ◽  
Jamie M. Moore ◽  
Alex Saidi ◽  
Catherine M. Feintuch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Plasmodium Yoelii ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Type I Ifn ◽  
Prime Type

scholarly journals Type I Interferon Inhibition and Dendritic Cell Activation during Gammaherpesvirus Respiratory Infection

2007 ◽  
Vol 81 (18) ◽  
pp. 9778-9789 ◽  
Author(s):  
Janet L. Weslow-Schmidt ◽  
Nancy A. Jewell ◽  
Sara E. Mertz ◽  
J. Pedro Simas ◽  
Joan E. Durbin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
The Body ◽  
Type I ◽  
Type I Ifn ◽  
Dendritic Cell Activation ◽  
Murine Gammaherpesvirus

ABSTRACT The respiratory tract is a major mucosal site for microorganism entry into the body, and type I interferon (IFN) and dendritic cells constitute a first line of defense against viral infections. We have analyzed the interaction between a model DNA virus, plasmacytoid dendritic cells, and type I IFN during lung infection of mice. Our data show that murine gammaherpesvirus 68 (γHV68) inhibits type I IFN secretion by dendritic cells and that plasmacytoid dendritic cells are necessary for conventional dendritic cell maturation in response to γHV68. Following γHV68 intranasal inoculation, the local and systemic IFN-α/β response is below detectable levels, and plasmacytoid dendritic cells are activated and recruited into the lung with a tissue distribution that differs from that of conventional dendritic cells. Our results suggest that plasmacytoid dendritic cells and type I IFN have important but independent roles during the early response to a respiratory γHV68 infection. γHV68 infection inhibits type I IFN production by dendritic cells and is a poor inducer of IFN-α/β in vivo, which may serve as an immune evasion strategy.

scholarly journals Dysregulated miRNome of plasmacytoid dendritic cells from patients with Sjögren’s syndrome is associated with processes at the centre of their function

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2305-2314 ◽  
Author(s):  
Maarten R Hillen ◽  
Eleni Chouri ◽  
Maojie Wang ◽  
Sofie L M Blokland ◽  
Sarita A Y Hartgring ◽  
...  
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
Mammalian Target Of Rapamycin ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Large Set ◽  
Type I Ifn ◽  
Stable Isotope Labelling ◽  
Proteomic Approach ◽  
Novel Targets

Abstract Objective A considerable body of evidence supports a role for type-I IFN in the pathogenesis of primary SS (pSS). As plasmacytoid dendritic cells (pDCs) are a major source of type-I IFN, we investigated their molecular regulation by measuring expression of a large set of miRNAs. Methods pDCs were isolated from peripheral blood of pSS patients (n = 30) and healthy controls (n = 16) divided into two independent cohorts (discovery and replication). Screening of 758 miRNAs was assessed by an OpenArray quantitative PCR-based technique; replication of a set of identified miRNAs was performed by custom array. Functional annotation of miRNA targets was performed using pathway enrichment. Novel targets of miR-29a and miR-29c were identified using a proteomic approach (stable isotope labelling with amino acids in cell culture). Results In the discovery cohort, 20 miRNAs were differentially expressed in pSS pDCs compared with healthy control pDCs. Of these, differential expression of 10 miRNAs was confirmed in the replication cohort. The dysregulated miRNAs were involved in phosphoinositide 3-kinase-Ak strain transforming and mammalian target of rapamycin signalling, as well as regulation of cell death. In addition, a set of novel protein targets of miR-29a and miR-29c were identified, including five targets that were regulated by both miRs. Conclusion The dysregulated miRNome in pDCs of patients with pSS is associated with aberrant regulation of processes at the centre of pDC function, including type-I IFN production and cell death. As miR-29a and miR-29c are pro-apoptotic factors and several of the novel targets identified here are regulators of apoptosis, their downregulation in patients with pSS is associated with enhanced pDC survival.

scholarly journals Human cytomegalovirus suppresses type I interferon secretion by plasmacytoid dendritic cells through its interleukin 10 homolog

Virology ◽  
2009 ◽  
Vol 390 (2) ◽  
pp. 330-337 ◽  
Author(s):  
W.L. William Chang ◽  
Peter A. Barry ◽  
Richard Szubin ◽  
Dai Wang ◽  
Nicole Baumgarth
Keyword(s):  
Dendritic Cells ◽  
Human Cytomegalovirus ◽  
Type I Interferon ◽  
Interleukin 10 ◽  
Plasmacytoid Dendritic Cells ◽  
Type I

CS16-6. Plasmacytoid Dendritic Cells are infected by Epstein Barr virus and induces TLR- dependent type I IFN production

Cytokine ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 106
Author(s):  
Martina Severa ◽  
Elena Giacomini ◽  
Eleni Anastasiadou ◽  
Valerie Gafa ◽  
Fabiana Rizzo ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Epstein Barr Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Type I Ifn ◽  
Barr Virus ◽  
Epstein Barr ◽  
Dependent Type
Sign in / Sign up

Export Citation Format

Share Document