Molecular Characterization of Human Plasmacytoid Dendritic Cells
Department of Immunology, Unit 901, 7455 Fannin, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. Journal of Clinical Immunology
(Impact Factor: 3.18).
04/2009; 29(3):257-64. DOI: 10.1007/s10875-009-9284-x
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.
A detailed molecular description of pDCs helps us better define, understand, and track human pDCs in relation to their functions and physiological involvement.
Available from: Till Mathan
- "BST2 is expressed on human cancer cells, monocytes, and vascular endothelium in response to IFN-α (Figure 9) (160–162). Similar to BDCA-2, ILT7 forms a complex with FcεRIγ, which, when ligated activates an immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling pathway that dampens TLR-7 and 9-induced IFN-α and TNF-α production (163, 164). ILT7 is downregulated upon stimulation of the pDCs by CpG, HSV, or IL-3, suggesting that pDC maturation prior to entering the tumor site may partly protect it from this suppressive mechanism (159, 164, 165). "
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ABSTRACT: Plasmacytoid dendritic cells (pDCs) are a specific subset of naturally occurring dendritic cells, that secrete large amounts of Type I interferon and play an important role in the immune response against viral infection. Several studies have highlighted that they are also effective antigen presenting cells, making them an interesting target for immunotherapy against cancer. However, the modes of action of pDCs are not restricted to antigen presentation and IFN secretion alone. In this review we will highlight a selection of cell surface proteins expressed by human pDCs that may facilitate communication with other immune cells, and we will discuss the implications of these molecules for pDC-driven immune responses.
Available from: Janette Furuzawa-Carballeda
- "CD123+/IDO+ cells pDCs constitute only 0.2–0.8% of peripheral blood cells and represent a unique rather plastic, versatile, and important immune cell population capable of producing over 95% of IFN-I synthesized by peripheral blood mononuclear cells in response to viruses as well as nucleic acid-containing complexes from the host. In addition to IFN-I, human pDCs produce proinflammatory cytokines such as TNF-α and IL-6 in response to TLR activation . Manlapat et al. have recently shown that the secretion of INF-α is indispensable for high-level expression of IDO after B7·1/B7·2 ligation to CTLA-4 [32, 36, 37]. "
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To characterise and enumerate IDO(+) cells, Tregs, and T cell subsets in patients with ulcerative colitis (UC) and Crohn's disease (CD) with regard to their clinical activity.
Ten active UC (aUC), 10 inactive UC (iUC), 6 aCD, and 8 iCD patients and 10 healthy individuals were included in the study. Circulating Foxp3-, IDO-, IL-17A-, IL-4-, IFN- γ -, and IL-10-expressing CD4(+) T cells were quantitated by flow cytometry. Interleukin-17-expressing cells, CD25(+)/Foxp3(+) Tregs, and CD123(+)/IDO(+) plasmacytoid dendritic cells were evaluated in intestinal biopsies from 10 aUC, 6 aCD, and 10 noninflamed tissues.
All CD4(+) T subsets were increased in aIBD patients compared with healthy donors. Meanwhile, frequency of CD8 α (+)/CD16(+)/IDO(+), CD8 α (+)/CD56(+)/IDO(+), CD8 α (+)/CD80(+)/IDO(+), CD8 α (+)/CD123(+)/IDO(+) large granular nonlymphoid cells, and CCR6(+)/CD123(+)/IDO(+) plasmacytoid dendritic cells was higher in aIBD patients versus healthy donors or iIBD patients. Tissue IL-17A(+) cells were present in higher amounts in aIBD versus noninflamed controls. IDO- and Foxp3-expressing cells were increased in aUC versus aCD patients and noninflamed tissues.
The findings represent an original work in Mexican Mestizo patients with IBD. It shows that Tregs and IDO-expressing cells are increased with regard to disease activity. These cells could significantly shape inflammatory bowel disease pathophysiology, severity, and tolerance loss.
Available from: Natacha Merindol
- "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. "
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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.
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