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Int Immunol. 2008 Oct;20(10):1259-68. doi: 10.1093/intimm/dxn082. Epub 2008 Jul 24.

The role of DC-STAMP in maintenance of immune tolerance through regulation of dendritic cell function.

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  • 1Department of Cell Differentiation, Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.

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.

PMID:
18653699
[PubMed - indexed for MEDLINE]
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