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(American Journal of Pathology. 2002;161:1077-1086.)
© 2002 American Society for Investigative Pathology

Animal Model

Deletion of Decay-Accelerating Factor (CD55) Exacerbates Autoimmune Disease Development in MRL/lpr Mice

Takashi Miwa^*, Michael A. Maldonado, Lin Zhou^*, Xiujun Sun^*, Hong Yuan Luo, Dewei Cai, Victoria P. Werth, Michael P. Madaio, Robert A. Eisenberg and Wen-Chao Song^*

From the Department of Pharmacology,^* Center for Experimental Therapeutics; the Department of Medicine, Division of Rheumatology; the Department of Dermatology; and the Department of Medicine, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

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 anemia syndrome paroxysmal nocturnal hemoglobinuria, the in vivo biology of DAF is still 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-deficient female 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 to be expressed 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 skin lesions, 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.

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