TY - JOUR
T1 - Deletion of decay-accelerating factor (CD55) exacerbates autoimmune disease development in MRL/lpr mice
AU - Miwa, Takashi
AU - Maldonado, Michael A.
AU - Zhou, Lin
AU - Sun, Xiujun
AU - Luo, Hong Yuan
AU - Cai, Dewei
AU - Werth, Victoria P.
AU - Madaio, Michael P.
AU - Eisenberg, Robert A.
AU - Song, Wen Chao
N1 - Funding Information:
Supported by National Institutes of Health grant AI 44970 .
PY - 2002/9
Y1 - 2002/9
N2 - Decay-accelerating factor (DAF, CD55) is a glycosylphosphatidylinositol-anchored membrane protein that restricts complement activation on autologous cells. It is also a ligand for CD97, an activation-associated lymphocyte antigen with seven transmembrane domains. It is widely expressed on cells of both the hematopoietic and nonhematopoietic lineages. Although deficiency of DAF on human erythrocytes is associated with the hemolytic anemiasyndrome paroxysmal nocturnal hemoglobinuria, the in vivo biology of DAF isstill poorly understood. We addressed the in vivo function of DAF in a knockout mouse model and describe here that deletion of DAF exacerbates autoimmune disease development in MRL/lpr mice, a model for human systemic lupus erythematosus. Compared to DAF-sufficient littermate controls, DAF-deficientfemale MRL/lpr mice developed exacerbated lymphadenopathy and splenomegaly, higher serum anti-chromatin autoantibody levels, and aggravated dermatitis.Consistent with the phenotype of aggravated dermatitis in DAF-deficient mice, Northern and Western blots and immunofluorescence studies showed DAF tobeexpressed abundantly in the mouse skin, suggesting that it may play a particularly important role in this tissue. Histology and immunostaining demonstrated inflammatory infiltrate and focal C3 deposition in early skinlesions, mostly along the dermal-epidermal junction. These results reveal a protective function of DAF in the development of a systemic autoimmune syndrome and suggest that dysfunction or down-regulation of DAF may contribute to autoimmune disease pathogenesis and manifestation i.e.,
AB - Decay-accelerating factor (DAF, CD55) is a glycosylphosphatidylinositol-anchored membrane protein that restricts complement activation on autologous cells. It is also a ligand for CD97, an activation-associated lymphocyte antigen with seven transmembrane domains. It is widely expressed on cells of both the hematopoietic and nonhematopoietic lineages. Although deficiency of DAF on human erythrocytes is associated with the hemolytic anemiasyndrome paroxysmal nocturnal hemoglobinuria, the in vivo biology of DAF isstill poorly understood. We addressed the in vivo function of DAF in a knockout mouse model and describe here that deletion of DAF exacerbates autoimmune disease development in MRL/lpr mice, a model for human systemic lupus erythematosus. Compared to DAF-sufficient littermate controls, DAF-deficientfemale MRL/lpr mice developed exacerbated lymphadenopathy and splenomegaly, higher serum anti-chromatin autoantibody levels, and aggravated dermatitis.Consistent with the phenotype of aggravated dermatitis in DAF-deficient mice, Northern and Western blots and immunofluorescence studies showed DAF tobeexpressed abundantly in the mouse skin, suggesting that it may play a particularly important role in this tissue. Histology and immunostaining demonstrated inflammatory infiltrate and focal C3 deposition in early skinlesions, mostly along the dermal-epidermal junction. These results reveal a protective function of DAF in the development of a systemic autoimmune syndrome and suggest that dysfunction or down-regulation of DAF may contribute to autoimmune disease pathogenesis and manifestation i.e.,
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U2 - 10.1016/S0002-9440(10)64268-X
DO - 10.1016/S0002-9440(10)64268-X
M3 - Article
C2 - 12213736
AN - SCOPUS:0036735306
SN - 0002-9440
VL - 161
SP - 1077
EP - 1086
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -