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© The Rockefeller University Press, 0022-1007/1997/11/1451/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 9, November 3, 1997 1451-1459

Article

Antinuclear Autoantibodies and Lupus Nephritis in Transgenic Mice Expressing Interferon {gamma} in the Epidermis

John P. Seery*, Joseph M. Carroll*, Victoria Cattell{ddagger}, and Fiona M. Watt*

From the * Keratinocyte Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; and the {ddagger} Department of Histopathology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London WC2A 3PX, United Kingdom

Systemic lupus erythematosus (SLE) is a potentially fatal non–organ-specific autoimmune disease that predominantly affects women. Features of the disease include inflammatory skin lesions and widespread organ damage caused by deposition of anti-dsDNA autoantibodies. The mechanism and site of production of these autoantibodies is unknown, but there is evidence that interferon (IFN) {gamma} plays a key role. We have used the involucrin promoter to overexpress IFN-{gamma} in the suprabasal layers of transgenic mouse epidermis. There was no evidence of organ-specific autoimmunity, but transgenic animals produced autoantibodies against dsDNA and histones. Autoantibody levels in female mice were significantly higher than in male transgenic mice. Furthermore, there was IgG deposition in the glomeruli of all female mice and histological evidence of severe proliferative glomerulonephritis in a proportion of these animals. Our findings are consistent with a central role for the skin immune system, acting under the influence of IFN-{gamma}, in the pathogenesis of SLE.

Address correspondence to Dr. Fiona M. Watt, Keratinocyte Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Phone: 44-171-269-3528; FAX: 44-171-269-3078. Joseph M. Carroll's current address is Genetics Institute, Andover, MA 01810.

J.P. Seery was supported by funds from Bristol-Myers Squibb and a European Union Biomed Network.

1 Abbreviations used in this paper: ENA, extractable nuclear antigens; GN, glomerulonephritis; HRP, horseradish peroxidase.


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