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, Wen Chao Song

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

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.,

Original languageEnglish (US)
Pages (from-to)1077-1086
Number of pages10
JournalAmerican Journal of Pathology
Volume161
Issue number3
DOIs
StatePublished - Jan 1 2002

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Inbred MRL lpr Mouse
CD55 Antigens
Dermatitis
Autoimmune Diseases
Paroxysmal Hemoglobinuria
Glycosylphosphatidylinositols
Skin
Complement Activation
Splenomegaly
Lymphocyte Activation
Knockout Mice
Northern Blotting
Systemic Lupus Erythematosus
Autoantibodies
Chromatin
Fluorescent Antibody Technique
Histology
Membrane Proteins
Down-Regulation
Erythrocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Deletion of decay-accelerating factor (CD55) exacerbates autoimmune disease development in MRL/lpr mice. / Miwa, Takashi; Maldonado, Michael A.; Zhou, Lin; Sun, Xiujun; Luo, Hong Yuan; Cai, Dewei; Werth, Victoria P.; Madaio, Michael P.; Eisenberg, Robert A.; Song, Wen Chao.

In: American Journal of Pathology, Vol. 161, No. 3, 01.01.2002, p. 1077-1086.

Research output: Contribution to journalArticle

Miwa, T, Maldonado, MA, Zhou, L, Sun, X, Luo, HY, Cai, D, Werth, VP, Madaio, MP, Eisenberg, RA & Song, WC 2002, 'Deletion of decay-accelerating factor (CD55) exacerbates autoimmune disease development in MRL/lpr mice', American Journal of Pathology, vol. 161, no. 3, pp. 1077-1086. https://doi.org/10.1016/S0002-9440(10)64268-X
Miwa, Takashi ; Maldonado, Michael A. ; Zhou, Lin ; Sun, Xiujun ; Luo, Hong Yuan ; Cai, Dewei ; Werth, Victoria P. ; Madaio, Michael P. ; Eisenberg, Robert A. ; Song, Wen Chao. / Deletion of decay-accelerating factor (CD55) exacerbates autoimmune disease development in MRL/lpr mice. In: American Journal of Pathology. 2002 ; Vol. 161, No. 3. pp. 1077-1086.
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