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

Yumi Sawatani, Takeshi Miyamoto, Shigenori Nagai, Mikako Maruya, Jun Imai, Kana Miyamoto, Nobuyuki Fujita, Ken Ninomiya, Toru Suzuki, Ryotaro Iwasaki, Yoshiaki Toyama, Masanori Shinohara, Shigeo Koyasu, Toshio Suda

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21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1259-1268
Number of pages10
JournalInternational immunology
Volume20
Issue number10
DOIs
Publication statusPublished - 2008 Oct 6

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Keywords

  • Autoimmunity
  • Dentritic cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Sawatani, Y., Miyamoto, T., Nagai, S., Maruya, M., Imai, J., Miyamoto, K., Fujita, N., Ninomiya, K., Suzuki, T., Iwasaki, R., Toyama, Y., Shinohara, M., Koyasu, S., & Suda, T. (2008). The role of DC-STAMP in maintenance of immune tolerance through regulation of dendritic cell function. International immunology, 20(10), 1259-1268. https://doi.org/10.1093/intimm/dxn082