The role of DC-STAMP in maintenance of immune tolerance through regulation of dendritic cell function.
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.
Sawatani
Yumi
Y
Department of Cell Differentiation, Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
Miyamoto
Takeshi
T
Nagai
Shigenori
S
Maruya
Mikako
M
Imai
Jun
J
Miyamoto
Kana
K
Fujita
Nobuyuki
N
Ninomiya
Ken
K
Suzuki
Toru
T
Iwasaki
Ryotaro
R
Toyama
Yoshiaki
Y
Shinohara
Masanori
M
Koyasu
Shigeo
S
Suda
Toshio
T
D000367:Age Factors; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000235:genetics; D017951:Antigen Presentation; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology; D013163:Splenomegaly / Q000097:blood / Q000235:genetics; D013601:T-Lymphocytes / Q000473:pathology; D015854:Up-Regulation
D000974:Antibodies, Antinuclear; C499636:DC-STAMP protein, mouse; D006183:H-2 Antigens; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010047:Ovalbumin