BDCA-2, a Novel Plasmacytoid Dendritic Cell–specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon α/β Induction
Andrzej Dzionek,Yoshiaki Sohma,Jun Nagafune,Marina Cella,Marco Colonna,Fabio Facchetti,Gritt Günther,C. Ian Johnston,Antonio Lanzavecchia,Tomoko Nagasaka,Tsutomu Okada,William Vermi,Gregor Winkels,Terumi Yamamoto,Monika Zysk,Yasunori Yamaguchi,Jürgen Schmitz +16 more
TLDR
Triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon alpha/beta in systemic lupus erythematosus patients.Abstract:
Plasmacytoid dendritic cells are present in lymphoid and nonlymphoid tissue and contribute substantially to both innate and adaptive immunity. Recently, we have described several monoclonal antibodies that recognize a plasmacytoid dendritic cell-specific antigen, which we have termed BDCA-2. Molecular cloning of BDCA-2 revealed that BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell–associated C-type lectin 2. Anti–BDCA-2 monoclonal antibodies are rapidly internalized and efficiently presented to T cells, indicating that BDCA-2 could play a role in ligand internalization and presentation. Furthermore, ligation of BDCA-2 potently suppresses induction of interferon α/β production in plasmacytoid dendritic cells, presumably by a mechanism dependent on calcium mobilization and protein-tyrosine phosphorylation by src-family protein-tyrosine kinases. Inasmuch as production of interferon α/β by plasmacytoid dendritic cells is considered to be a major pathophysiological factor in systemic lupus erythematosus, triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon α/β in systemic lupus erythematosus patients.read more
Citations
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Tolerogenic dendritic cells.
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Plasmacytoid dendritic cells in immunity.
TL;DR: Recent progress on the characterization of plasmacytoid dendritic cell origin, development, migration and function in immunity and tolerance, as well as their effect on human diseases are reviewed.
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Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance
Laura Bonifaz,David P. Bonnyay,Karsten Mahnke,Karsten Mahnke,Miguel Rivera,Michel C. Nussenzweig,Michel C. Nussenzweig,Ralph M. Steinman +7 more
TL;DR: DEC-205 provides an efficient receptor-based mechanism for dendritic cells to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.
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Dendritic cells as therapeutic vaccines against cancer
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Jacques Banchereau,Francine Brière,Christophe Caux,Jean Davoust,Serge Lebecque,Yong-Jun Liu,Bali Pulendran,Karolina Palucka +7 more
TL;DR: Dendritic cells are antigen-presenting cells with a unique ability to induce primary immune responses and may be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response.
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Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products.
TL;DR: The capacity of DCs to capture and process antigen could be modulated by exogenous stimuli was investigated and it was found that DCs respond to tumor necrosis factor alpha, CD40 ligand, IL-1, and lipopolysaccharide with a coordinate series of changes that include downregulation of macropinocytosis and Fc receptors, disappearance of the class II compartment, and upregulation of adhesion and costimulatory molecules.
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Frederick P. Siegal,Norimitsu Kadowaki,Michael Shodell,Patricia Fitzgerald-Bocarsly,Kokila Shah,Stephen Ho,Svetlana Antonenko,Yong-Jun Liu +7 more
TL;DR: Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge and are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
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Reciprocal Control of T Helper Cell and Dendritic Cell Differentiation
Marie-Clotilde Rissoan,Vassili Soumelis,Norimitsu Kadowaki,Géraldine Grouard,Francine Brière,Rene de Waal Malefyt,Yong-Jun Liu +6 more
TL;DR: A negative feedback loop from the mature T helper cells may selectively inhibit prolonged TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset.
Journal ArticleDOI
Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon.
Marina Cella,David Jarrossay,Fabio Facchetti,Olga Alebardi,Hideo Nakajima,Antonio Lanzavecchia,Marco Colonna +6 more
TL;DR: Results, with the distinct cell phenotype, indicate that plasmacytoid monocytes represent a specialized cell lineage that enters inflamed lymph nodes at high endothelial venules, where it produces type I interferon.