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International Immunology Advance Access originally published online on July 24, 2008
International Immunology 2008 20(10):1259-1268; doi:10.1093/intimm/dxn082
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Yumi Sawatani1,2,*, Takeshi Miyamoto1,3,4,5,*, Shigenori Nagai6,7, Mikako Maruya6,7, Jun Imai6,7, Kana Miyamoto1, Nobuyuki Fujita1,3, Ken Ninomiya1,3, Toru Suzuki1,3, Ryotaro Iwasaki1,8, Yoshiaki Toyama3, Masanori Shinohara2, Shigeo Koyasu6,7 and Toshio Suda1

1 Department of Cell Differentiation, Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
2 Department of Dentistry and Oral Surgery, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan
3 Department of Orthopedic Surgery
4 Department of Musculoskeletal Reconstruction and Regeneration Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
5 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
6 Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
7 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
8 Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Correspondence to: T. Miyamoto; E-mail: miyamoto{at}sc.itc.keio.ac.jp

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.

Keywords: autoimmunity, dentritic cells

* These authors contributed equally to this work.

Transmitting editor: K. Inaba

Received 28 December 2007, accepted 27 June 2008.


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