Molecular characterization of human plasmacytoid dendritic cells.
ABSTRACT INTRODUCTION: Plasmacytoid dendritic cells (pDCs) represent a unique and important immune cell population capable of producing large quantifies of type I interferon (IFN) in response to viruses as well as nucleic acid-containing complexes from the host. These rare and mysterious cells have been revealed by in-depth molecular characterization. Several innate sensors and signaling molecules enriched in pDCs allow their specialized innate immune functions. In addition, human pDCs use a group of surface receptors that, through activation of a B-cell receptor (BCR)-like signaling pathway, modulate type I IFN responses. It is clear now that pDC development is influenced by distinctive transcription factors that specify a unique lineage. CD4(+)CD56(+) hematodermic neoplasm of human pDC origin has been revealed in explicit molecular terms. CONCLUSION: A detailed molecular description of pDCs helps us better define, understand, and track human pDCs in relation to their functions and physiological involvement.
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- "c o m / l o c a t e / y c i m m the unique immune properties of UCB, and open new avenues for improving UCB transplantation outcome. PDC selectively express Toll-like receptors 7 and 9 (TLR-7 and TLR-9), which are localized in the endosomal–lysosomal compartment and recognize unmethylated CpG motifs on viral RNA and DNA . Upon activation by TLR-ligands, adult PDC rapidly secrete massive amounts of type I interferons (IFN) as well as chemokines that allow for the recruitment and the activation of immune cells. "
ABSTRACT: Plasmacytoid dendritic cells (PDCs) from human umbilical cord blood (UCB) produce lower amounts of IFN-α upon TLR stimulation compared with adult counterparts. This difference may play a role in the low graft-versus-host disease rate after UCB transplantation and in the impaired immune response of the neonate to pathogens. Comparing UCB PDC to their adults counterparts, we found that they exhibited a mature surface phenotype and a normal antigen uptake. They upregulated costimulatory molecules upon activation, although with delayed kinetics. Protein, but not ARN, levels of TLR-9, MyD88, IRAK1 and IRF-7, involved in the TLR-9 signaling pathway were reduced. The expression levels of miR-146a and miR-155, known to be involved in the post-transcriptional down-regulation of immune responses, were higher. These data point out a post-transcriptional down-regulation of the TLR-9/IRF-7 signaling pathway in UCB PDC.Cellular Immunology 04/2012; 276(1-2):114-21. DOI:10.1016/j.cellimm.2012.04.010 · 1.87 Impact Factor
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ABSTRACT: Skin immune surveillance is granted by a complex contingent of sentinel innate immune cells with antigen-presenting function. The latter include Langerhans cells (LCs), multiple subsets of dermal dendritic cells (DDCs), and dermal macrophages (DMs). As for other peripheral nonlymphoid tissues, the microenvironment of the normal skin is lacking plasmacytoid dendritic cells (PDCs), a circulating DCs subset that mainly populates primary and secondary lymphoid organs. PDCs accumulation in the skin is observed in different cutaneous inflammatory disorders, including autoimmunity and viral infection. This review will summarize current knowledge on the biology of skin DCs and will highlight the functional role of PDCs in the complex microenvironment of well-characterized cutaneous disease models.03/2012; 2(1). DOI:10.1007/s13671-012-0033-7
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ABSTRACT: Plasmacytoid dendritic cells (pDCs) are specialized dendritic cells (DCs) that produce large amounts of type I interferon (IFN) after Toll-like receptor (TLR) activation. Human pDCs preferentially express immunoglobulin-like transcript 7 (ILT7; LILRA4), which couples with a signaling adapter to activate a prominent immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling pathway. ILT7 protein directly binds to and can be activated by bone marrow stromal cell antigen 2 (BST2; CD317) protein, the expression of which is found on cells pre-exposed to IFN or on the surface of human cancer cells. The interaction between ILT7 and BST2 functions to assure an appropriate TLR response by pDCs during viral infection and likely participates in pDC-tumor crosstalk. Two opposing modes of receptor-mediated regulatory mechanisms work jointly to fine tune the innate immunity of pDCs.Immunological Reviews 03/2010; 234(1):163-76. DOI:10.1111/j.0105-2896.2009.00867.x · 12.91 Impact Factor