TY - JOUR
T1 - The role of DC-STAMP in maintenance of immune tolerance through regulation of dendritic cell function
AU - Sawatani, Yumi
AU - Miyamoto, Takeshi
AU - Nagai, Shigenori
AU - Maruya, Mikako
AU - Imai, Jun
AU - Miyamoto, Kana
AU - Fujita, Nobuyuki
AU - Ninomiya, Ken
AU - Suzuki, Toru
AU - Iwasaki, Ryotaro
AU - Toyama, Yoshiaki
AU - Shinohara, Masanori
AU - Koyasu, Shigeo
AU - Suda, Toshio
N1 - Funding Information:
Grant-in-aid for Young Scientists (B) Japan, Japan Society for the Promotion of Science Fujita Memorial Fund for Medical Research, Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Mochida Memorial Foundation for Medical and Pharmaceutical Research to T.M; grant-in-aid from Specially Promoted Research of the Ministry of Education, Science, Sports and Culture, Japan to T.S.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/52949098785
UR - https://www.scopus.com/pages/publications/52949098785#tab=citedBy
U2 - 10.1093/intimm/dxn082
DO - 10.1093/intimm/dxn082
M3 - Article
C2 - 18653699
AN - SCOPUS:52949098785
SN - 0953-8178
VL - 20
SP - 1259
EP - 1268
JO - International Immunology
JF - International Immunology
IS - 10
ER -