Animal models of cutaneous lupus erythematosus and lupus erythematosus photosensitivity.
Over the past decade, the most exciting and important finding in SLE-prone mice is the discovery of Fas/Fas ligand systems in the pathogenesis of autoimmune phenomena. A human model for murine lpr/gld disease has also been reported recently. Furthermore, as shown in Table 2, studies on Ig variable region genes, TCR genes and MHC class II genes have given us much information concerning human and murine SLE. With respect to cytokines, IL-2 deficiency and the key role of IL-6 have been found in SLE-prone mouse strains, and Th2 cytokine production has been demonstrated to play a more pathogenic role than Th1 cytokine production in human and murine SLE except for MRL/pr mice. TGF is also very intriguing because TGF-beta knockout mice show SLE-like autoantibodies and Sjögren syndrome-like lymphoproliferation. Apart from these basic scientific investigations, there are also many promising and practical therapeutic approaches. In particular, treatments with anti-CD4 antibody and murine CTLA4Ig which bound B7 and blocked binding of CD28 to B7 are outstanding. However, it remains obscure whether such new approaches are effective for the skin lesions of SLE-prone mice, although some immunosuppressive agents such as FK506, cyclosporin and Chinese herbal medicines have been evaluated to determine their selective effects on the skin lesions of MRL/lpr mice. Needless to say, mouse models are not identical, but similar, to human diseases. However, they are important in the search for the underlying pathogenesis of autoimmune diseases on the basis of careful evaluation of the similarities and differences between human diseases and these models. If such studies are steadily performed, then inbred or experimental models will become more promising tools for the investigation of cutaneous lupus erythematosus.
Furukawa
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Department of Dermatology, Hamamatsu University School of Medicine, Japan.
D000818:Animals; D004195:Disease Models, Animal; D008178:Lupus Erythematosus, Cutaneous / Q000150:complications / Q000503:physiopathology*; D051379:Mice; D016513:Mice, SCID; D010787:Photosensitivity Disorders / Q000209:etiology / Q000503:physiopathology*