Abstract
Regulation of dendritic cell (DC) function is critical for maintaining self-tolerance and preventing autoimmunity. The dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in cell-cell fusion of osteoclasts and foreign body giant cells, but though originally identified in DCs, its specific roles there remain undefined. Here, we report that aged DC-STAMP-deficient mice display several systemic autoimmune symptoms such as spontaneous lymphoproliferation, splenomegaly associated with infiltration of T cells in several organs and increased serum anti-double-stranded DNA antibody production. Although a lack of DC-STAMP did not inhibit DC differentiation or proliferation, antigen presentation activity of DC-STAMP-deficient DCs was significantly up-regulated in both class I and II pathways through increased phagocytotic activity compared with wild-type DCs, an activity likely leading to autoimmunity. Our results indicate that DC-STAMP is required for proper regulation of DC activity and maintenance of immune self-tolerance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Age Factors
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Animals
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Antibodies, Antinuclear / blood
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Antibodies, Antinuclear / genetics
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Antigen Presentation*
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Autoimmunity / genetics
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Autoimmunity / immunology*
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Cell Movement / genetics
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Cell Movement / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / pathology
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H-2 Antigens / genetics
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H-2 Antigens / immunology
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H-2 Antigens / metabolism
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Immunity, Cellular / genetics
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Lymphocyte Activation / genetics
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Membrane Proteins* / genetics
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Membrane Proteins* / immunology
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Membrane Proteins* / metabolism
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Mice
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Mice, Knockout
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Mice, Transgenic
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Nerve Tissue Proteins* / genetics
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Nerve Tissue Proteins* / immunology
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Nerve Tissue Proteins* / metabolism
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Ovalbumin
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Phagocytosis / genetics
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Phagocytosis / immunology*
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Self Tolerance / genetics
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Self Tolerance / immunology
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Splenomegaly / blood
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Splenomegaly / genetics
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T-Lymphocytes / pathology
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Up-Regulation
Substances
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Antibodies, Antinuclear
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DC-STAMP protein, mouse
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H-2 Antigens
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Membrane Proteins
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Nerve Tissue Proteins
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Ovalbumin