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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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.Frontiers in Immunology 11/2013; 4:372. DOI:10.3389/fimmu.2013.00372
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ABSTRACT: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy derived from precursors of plasmacytoid dendritic cells. Very few cases of BPDCN have been described with lack of skin manifestations at the time of diagnosis. Here we report two rare non-cutaneous presentations of BPDCN without obvious skin lesions at our institution and also the literature review. Our first patient had a unique presentation of BPDCN confined to the sinonasal region with central nervous system involvement. The second patient we report is also atypical with regard to widespread disease that uncharacteristically spared the skin and bone marrow. BPDCN is a rare hematological malignancy involving immature plasmacytoid dendritic cells. It poses a diagnostic challenge requiring multidisciplinary approach to manage this disease. It is important to identify effective therapies for both cutaneous and non-cutaneous presentations of BPDCN, since most cases are uniformly fatal with conventional chemotherapy alone. High-dose induction therapy based on acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) regimens, to achieve complete remission followed by allo-hematopoietic stem cell transplantation from related or unrelated donors is recommended to improve long-term survival in these patients. Larger scale studies are warranted to understand the pathophysiology of the disease and the important prognostic indicators for optimal management. Copyright © 2014 John Wiley & Sons, Ltd.Hematological Oncology 05/2014; DOI:10.1002/hon.2147 · 2.36 Impact Factor
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ABSTRACT: Plasmacytoid dendritic cells (pDC) have been regarded as the "professional type I IFN-producing cells" of the immune system following viral recognition that relies on the expression of TLR7 and TLR9. Furthermore, pDC link the innate and adaptive immune systems via cytokine production and Ag presentation. More recently, their ability to induce tolerance and cytotoxicity has been added to their "immune skills." Such a broad range of actions, resembling the diverse functional features of a Swiss army knife, requires strong and prompt molecular regulation to prevent detrimental effects, including autoimmune pathogenesis or tumor escape. Over the last decades, we and other investigators have started to unravel some aspects of the signaling pathways that regulate the various functions of human pDC. In this article, we review aspects of the molecular regulatory mechanisms to control pDC function in light of their multifaceted roles during immunity, autoimmunity, and cancer. Copyright © 2014 by The American Association of Immunologists, Inc.The Journal of Immunology 12/2014; 193(12):5772-5778. DOI:10.4049/jimmunol.1401541 · 5.36 Impact Factor