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

被引:30
|
作者
Sawatani, Yumi [1 ,2 ]
Miyamoto, Takeshi [1 ,3 ,4 ,5 ]
Nagai, Shigenori [6 ,8 ]
Maruya, Mikako [6 ,8 ]
Imai, Jun [6 ,8 ]
Miyamoto, Kana [1 ]
Fujita, Nobuyuki [1 ,4 ]
Ninomiya, Ken [1 ,4 ]
Suzuki, Toru [1 ,4 ]
Iwasaki, Ryotaro [1 ,7 ]
Toyama, Yoshiaki [4 ]
Shinohara, Masanori [2 ]
Koyasu, Shigeo [6 ,8 ]
Suda, Toshio [1 ]
机构
[1] Keio Univ, Sch Med, Sakaguchi Lab Dev Biol, Dept Cell Differentiat,Shinjuku Ku, Tokyo 1608582, Japan
[2] Kumamoto Univ, Sch Med, Dept Dent & Oral Surg, Kumamoto 8608556, Japan
[3] Keio Univ, Sch Med, Dept Musculoskeletal Reconstruct & Regenerat Surg, Shinjuku Ku, Tokyo 1608582, Japan
[4] Keio Univ, Sch Med, Dept Orthoped Surg, Shinjuku Ku, Tokyo 1608582, Japan
[5] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan
[6] Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo 1608582, Japan
[7] Keio Univ, Sch Med, Dept Dent & Oral Surg, Shinjuku Ku, Tokyo 1608582, Japan
[8] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Kawaguchi, Saitama 3320012, Japan
基金
日本科学技术振兴机构;
关键词
autoimmunity; dentritic cells;
D O I
10.1093/intimm/dxn082
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1259 / 1268
页数:10
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