IFN-gamma transgenic mice: clues to the pathogenesis of systemic lupus erythematosus?

Transgenic mice overexpressing IFN-gamma in the epidermis develop an inflam matory skin disease resembling cutaneous lupus erythematosus shortly after birth. By 3 months of age, most female transgenics develop a lupus-like syn drome characterised by production of IgG anti-dsDNA, antihistone and antinu cleosome autoantibodies. The autoantibodies are nephritogenic, with one-thi rd of females developing a severe immune complex mediated glomerulonephriti s. Analysis of these transgenics suggests that pathogenic autoantibodies ar ise via an antigen-driven T-cell-dependent mechanism with apoptotic keratin ocytes acting as a potential source of autoantigen. The mechanism of autoan tibody production in IFN-gamma transgenics may be relevant to human lupus a nd is consistent with a central role for cutaneous T cells in the pathogene sis of systemic lupus erythematosus in man.