The last 20 years produced extraordinary insights into all aspects of pdc biology, including. Jan 01, 2009 dendritic cells dcs are the most efficient antigenpresenting cells apcs because of their ability to capture, process, and present antigens to naive t lymphocytes. Activated pdcs link innate immunity and adaptive immunity to viruses. Plasmacytoid dendritic cells pdcs play a crucial role in antiviral innate immunity through their unique capacity to produce large amounts of type i. Plasmacytoid dendritic cells are a unique dendritic cell subset that bridges innate and adaptive immune responses. Plasmacytoid dendritic cells orchestrate innate and. Mar 31, 2010 a variety of different vaccine types are available for h1n1 influenza a virus infections. Dendritic cells dcs, named for their probing, treelike or dendritic shapes, are responsible for the initiation of adaptive immune responses and hence function as the sentinels of the immune system. Plasmacytoid dendritic cells pdcs play a crucial role in triggering antiviral immunity through their ability to capture and process viral antigens and subsequently induce adaptive immune responses. Therefore, restoring functional antihbv immunity is a promising immunotherapeutic approach to treatment of chronic infection. Plasmacytoid dendritic cells pdcs resemble antibodysecreting plasma cells and are believed to arise from a lymphoid progenitor.
Imaging of plasmacytoid dendritic cell interactions with t. The function of pdcs as the professional type i ifnproducing cells is linked to their selective expression of tolllike receptor 7 tlr7 and tlr9, which sense viral nucleic acids within the endosomal. Cells free fulltext human plasmacytoid dendritic cells. Yet, there is increasing evidence that pdcs are a distinct cell type in the innate immune system. Plasmacytoid dendritic cells pdcs are a rare type of immune cell that are known to secrete large quantities of type 1 interferon ifns in response to a viral infection. We studied the subsets of peripheral blood dendritic cells dcs and lipid accumulation in dcs to investigate the involvement of dcs in the decreased anticancer immunity of advanced lung cancer patients. Plasmacytoid dendritic cells pdcs, as well as myeloid dendritic cells mdcs, have a dual role not only in initiating immune responses but also in inducing tolerance to exogenous and endogenous antigens. Given that plasmacytoid dendritic cells pdcs are key to the pathogenesis of lupus, we investigated the properties of pdcs from nzb and nzw mice. They are a heterogeneous cell population, where plasmacytoid dendritic cells pdcs are a unique subset capable of secreting high levels of type i ifns.
Plasmacytoid dendritic cells pdcs, referred to as natural interferon ifnproducing cells ipcs, were originally discovered in humans as a small subset of blood leukocytes specialized in the secretion of high amounts of type i ifn in response to viruses, and the murine counterparts of human ipcs were identified on the basis of their. Imaging of plasmacytoid dendritic cell interactions with t cells. Plasmacytoid dendritic cells induce efficient stimulation of. Adaptive immune responses develop against an array of potential antigens presented to effector t lymphocytes by antigenpresenting cells, especially dendritic cells. The major type i interferonproducing plasmacytoid dendritic cells pdc surround and infiltrate certain tumors like malignant melanoma, head and neck cancer, and ovarian and breast cancer. Plasmacytoid dendritic cells are crucial for the initiation. To understand this negative impact of tumorassociated pdc tapdc, we developed an orthotopic murine mammary tumor model that closely mimics the human pathology. Plasmacytoid dendritic cells induce plasma cell differentiation. Upon further examination of the cellular mechanisms responsible for cva21induced antitumor immunity we have identified the importance of type i ifn for nk cell activation, and demonstrated that both icam1 and plasmacytoid dendritic cells were key. Plasmacytoid dendritic cell function was investigated using depletion experiments by injecting b. Plasmacytoid dendritic cell precursors pdcipc are the major producers of type i interferon and have the unique ability to link innate and adaptive immunity. Immunity article plasmacytoid dendritic cells are crucial for the initiation of in.
Dendritic cells dcs are essential antigenpresenting cells for the induction of t cell immunity against pathogens such as human immunodeficiency virus hiv1. Frontiers diseaseassociated plasmacytoid dendritic cells. Plasmacytoid dendritic cells in immunity nature immunology. Although pdcs produce cytokines such as typei ifns, tnf. Dcs are bone marrow bmderived leukocytes and are the most potent. Plasmacytoid dendritic cells pdcs play a crucial role in antiviral innate immunity through their unique capacity to produce large amounts of type i interferons ifns upon viral detection.
Human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts of type i interferons in response to viruses, the socalled natural interferonproducing cells. Physiological role of plasmacytoid dendritic cells and their. They develop from bone marrow hematopoietic stem cells and constitute nov 17, 2004 human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts of type i interferons in response to viruses, the socalled. Prospect of plasmacytoid dendritic cells in enhancing anti. Plasmacytoid dendritic cells in atherosclerosis circulation. Among immune cells involved in cancer immunity, properly activated plasmacytoid dendritic cells pdcs exert an important role, bridging the innate and adaptive immune responses and directly eliminating cancer cells. Here, we show that plasmacytoid dendritic cells pdcs and type i interferon ifnmediated signaling delineate the immunogenicity of live attenuated virus, inactivated wholevirus wv, and splitvirus vaccines. Plasmacytoid dendritic cell an overview sciencedirect topics.
Combined with their antigen presentation capacity, this powerful functionality enables pdcs to orchestrate innate and adaptive immune responses. Upon activation by synthetic tolllike receptor agonists or viruses. At the same time, hiv1 replication is strongly enhanced in dct. Human plasmacytoid dendritic cells are equipped with antigen. Plasmacytoid dendritic cells pdcs have been associated with several names and functions over time, reflecting the limited availability of specific markers and their ability to produce large amounts of type i interferons, present antigens, as well as prime disparate tcell helper responses.
Plasmacytoid dendritic cells pdcs represent a unique and crucial immune cell population capable of producing large amounts of type i interferons ifns in response to viral infection. Plasmacytoid dendritic cells from parent strains of the nzbw. Plasmacytoid dendritic cells pdcs are innate immune sentinels that play important roles in immunity to infection and autoimmunity. Aug 20, 2008 dendritic cells dcs play a pivotal role in the control of innate and adaptive immune responses. Plasmacytoid dendritic cells pdcs are a particular subset of dcs that link innate and adaptive immunity. Plasmacytoid dendritic cells pdcs are specialized in rapid and massive secretion of type i interferon ifn. Plasmacytoid dendritic cells pdcs are innate immune cells that produce type i interferon ifni and other cytokines in response to virusderived nucleic acids. Human plasmacytoid dendritic cells are equipped with. Plasmacytoid dendritic cells pdcs, also called natural interferon producing cells ipcs represent a specialized cell type within the innate immune system. Notably, all these responses are highly dependent on the fitness of the host immune system, including the innate compartment.
Dendritic cells dcs form a remarkable cellular network that shapes adaptive immune responses according to peripheral cues. Human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts of type i interferons in. After four decades of research, we now know that dcs arise from a hematopoietic lineage distinct from other leukocytes, establishing the dc system as a unique hematopoietic branch. Dendritic cells dcs link innate immune sensing of the environment to the initiation of adaptive immune responses. To understand this negative impact of tumorassociated pdc tapdc, we developed an orthotopic murine mammary tumor model. Tolerogenic and activatory plasmacytoid dendritic cells in. Recent work has also established that tissue dcs consist of.
The importance of dendritic cells in maintaining immune tolerance. Both innate and adaptive immunity are involved in this process. Dendritic cells dcs play a pivotal role in the control of innate and adaptive immune responses. We therefore attempted to improve the antitumor effect by identifying littleknown key pathways in gmcsfsensitized dendritic cells. Human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts of type i interferons in response to viruses, the socalled. They are the only antigenpresenting cell capable of stimulating naive t cells, and hence they are pivotal in the generation of adaptive immunity.
Resident dcs that develop from thymic lymphoid pre cursors are the most abundant subset and. Plasmacytoid dendritic cells are crucial in bifidobacterium. Monocytic precursors of myeloid dcs, which favor a t. We then determined lipid accumulation in the dcs using bodipy 650665, a fluorophore with an. Vaccination with irradiated granulocyte macrophage colonystimulating factor gmcsftransduced autologous tumor cells gvax has been shown to induce therapeutic antitumor immunity. Plasmacytoid dendritic cells orchestrate innate and adaptive. Paul langerhans first described dcs in human skin in 1868 but thought they were cutaneous nerve cells.
A comprehensive evaluation of human plasmacytoid dendritic. Plasmacytoid dendritic cells pdcs constitute a unique dc subset specialized in rapid and massive secretion of cytokines, including type i interferon i. Tlr7 agonist 852a inhibition of tumor cell proliferation. Dendritic cells dc play an essential role in initiating and shaping antitumor immune responses. Dendritic cells dcs are the most efficient antigenpresenting cells apcs because of their ability to capture, process, and present antigens to naive t lymphocytes. Plasmacytoid dendritic cells control tcell response to. Elucidation of the role played by cells of the innate immune system, particularly the dendritic cell dc populations, has led to a precipitous growth in our understanding of immunity to pathogens and foreign antigens. They circulate in the blood and are found in peripheral lymphoid organs. Continuous expression of the transcription factor e22 maintains the cell fate of mature plasmacytoid dendritic cells. Potential functional role of plasmacytoid dendritic cells in. Pdf plasmacytoid dendritic cells in immunity researchgate. Human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts. We analyzed the population of dc subsets in peripheral blood using flow cytometry.
Plasmacytoid dendritic cells delineate immunogenicity of. Tumor promotion by intratumoral plasmacytoid dendritic. Here, we show that plasmacytoid dendritic cells pdcs and type i interferon ifnmediated signaling delineate the immunogenicity of live attenuated virus, inactivated wholevirus wv, and splitvirus. Lipidladen partiallyactivated plasmacytoid and cd4cd8. Mhc class iirestricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic t cell immunity.
Oct 16, 2017 plasmacytoid dendritic cells pdcs, also called natural interferon ifnproducing cells, represent a specialized cell type within the innate immune system. The presence of pdc in these tumors is associated with an unfavorable prognosis for the patients as long as these cells are unstimulated. A distinct subset of plasmacytoid dendritic cells induces. Plasmacytoid dendritic cells pdcs are 1 of 2 major subsets of human dcs that. Antitumor effects of the tolllike receptor 7 tlr7 agonist, 852a, were evaluated. Apr 14, 2016 plasmacytoid dendritic cells orchestrate tlr7mediated innate and adaptive immunity for the initiation of autoimmune inflammation skip to main content thank you for visiting. Lung cancers have been found to include four different subsets of dendritic cells. Human plasmacytoid dendritic cells pdcs represent a highly specialized naturally occurring dendritic cell subset and are the main producers of type i interferons ifns in response to viral infections.
Upon activation by synthetic tolllike receptor agonists. They are responsible for the substantial production of type 1 interferon ifni in response to viral rna or dna through activation of tlr7 and 9. They release high amounts of type i interferons in response to viral and bacterial infection. Antigen delivery to plasmacytoid dendritic cells induction of tolerance and immunity. Physiological role of plasmacytoid dendritic cells and. Plasmacytoid dendritic cells pdc are key regulators of antiviral immunity. Although many of the contributing genes have been identified, the contributing cellular abnormality associated with each parent strain remains unresolved. Adaptive t and b cells immunity and control by dendritic. Dendritic cells dcs are central regulators of the adaptive immune response, and as such are necessary for tcellmediated cancer immunity. Infections with persistent viruses are a frequent cause of immunosuppression, autoimmune sequelae, andor neoplastic disease. It has been demonstrated that pdcs can coordinate events during the course of viral infection, atopy, autoimmune diseases, and cancer.
Trim8 is required for virusinduced ifn response in human. Myeloid and plasmacytoid dendritic cells transfer hiv1. Plasmacytoid dendritic cells pdcs were first described as interferonproducing cells and, for many years, their overlapping characteristics with both lymphocytes and classical dendritic cells cdcs created confusion over their exact ontogeny. Given their supreme capacity to interact with and present antigen to t cells, dcs have been proposed as key mediators of immunological tolerance in the steady state. In particular, antitumoral responses depend on a specialized subset of conventional dcs that transport tumor antigens to draining lymph nodes and crosspresent antigen to activate cytotoxic t lymphocytes. Here we show a critical role for pdcs in t cellindependent ti iga production by b cells in the galt. Plasmacytoid dendritic cells in immunity researchgate. Upon further examination of the cellular mechanisms responsible for cva21induced antitumor immunity we have identified the importance of type i ifn for nk cell activation, and demonstrated that both icam1 and plasmacytoid dendritic cells were key mediators of this response. Much of this information has been derived from studies using mouse model systems. From plasmacytoid to dendritic cell wiley online library. Plasmacytoid dendritic cells support melanoma progression by.
Plasmacytoid dendritic cells induce efficient stimulation. The role of dendritic cells in shaping the immune response. Although both conventional dendritic cells cdcs and plasmacytoid dendritic cells pdcs are present in the gutassociated lymphoid tissues galt, the roles of pdcs in the gut remain largely unknown. Plasmacytoid dendritic cells from parent strains of the. Lipid accumulation in peripheral blood dendritic cells and. Tumor promotion by intratumoral plasmacytoid dendritic cells. Dendritic cells dcs initiate and control immune re cells resistant to further viral infection katze et al. Depending on their maturation state and on the microenvironment, pdcs can mediate immunity or tolerance. Furthermore, pdcs present antigens and induce naive t cell differentiation.
However, their role in tumor immunity is less clear. It has been demonstrated that pdcs can coordinate events during the course of viral infection, atopy. Plasmacytoid dendritic cells orchestrate innate and adaptive antitumor immunity induced by oncolytic coxsackievirus a21. Plasmacytoid dendritic cells in antiviral immunity and. Diseaseassociated plasmacytoid dendritic cells frontiers. The function of pdcs as the professional type i ifnproducing cells is linked to their selective expression of tolllike receptor 7 tlr7 and tlr9, which sense viral nucleic acids. Plasmacytoid dendritic cells pdcs are one of two principal subsets of human dendritic cells dcs.
Dendritic cells also interact with and influence the response of cells of the innate immune system. Tlr7 ligand augments gmcsfinitiated antitumor immunity. Linking innate and adaptive immunity kelli mckenna, annesophie beignon, and nina bhardwaj departments of pathology, dermatology, and medicine, nyu cancer institute, the new york university school of medicine, new york, new york plasmacytoid dendritic cells pdcs are one of two principal. In previous studies, we reported that pdcinfiltrating human primary breast tumors represent an independent prognostic factor associated with poor outcome. Supernatants from human peripheral blood mononuclear cells pbmc stimulated with 852a inhibited the proliferation of tumor cell lines hs294t and 769p but had no effect on others 786o and caki1. A variety of different vaccine types are available for h1n1 influenza a virus infections. Pdf human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts of type i. Plasmacytoid dendritic cells support melanoma progression. Depending on the context, pdc can both promote or suppress antitumor immune responses.
Plasmacytoid dendritic cells pdc, the major producers of type i interferon, are principally recognized as key mediators of antiviral immunity. On the basis of the ability of the plasmacytoid cells to induce t helper type 2 t. Recent work has also established that tissue dcs consist of developmentally and. They develop from bone marrow hematopoietic stem cells and constitute pdf. H2 cell differ entiation in response to certain stimuli, the name type 2 dc pre cursor pdc2 was proposed. Plasmacytoid dendritic cells are thought to act as key players in renal allograft rejection, but the underlying mechanisms are unclear. Development, regulation, and function boris reizis1, 1department of pathology and department of medicine, new york university school of medicine, new york, ny 10016, usa. Dendritic cells are central to the initiation of primary immune responses.
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