Involvement of a tissue-specific autoantibody in skin disorders of murine systemic lupus erythematosus and autoinflammatory diseases.
Human systemic lupus erythematosus (SLE) and its murine model, MRL lpr/lpr mice, are well known to develop a wide range of symptoms, such as glomerulonephritis, dermatitis, and arthritis, as an immune-complex disease. However, the deposition of circulating immune complex does not fully explain the tissue specificity of disease. Tissue-specific autoantigens may also be involved in tissue inflammation. In this study, desmoglein 3 (Dsg3), a major component of epidermal desmosomes, was identified as a skin-specific autoantigen. Several murine models of skin inflammation were found to develop autoantibodies to Dsg3 tightly correlated with disease aggravation, especially in MRL lpr/lpr mice. Furthermore, SLE-prone skin disease-free FcgammaRIIb-deficient mice developed skin inflammation upon immunization with Dsg3. Taken together with histological studies, we concluded that skin-specific Dsg3 serves as an autoantigen in chronic skin inflammatory diseases accompanied by mast cell degranulation, including both murine SLE and other autoinflammatory diseases.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.jlstrom@fas.harvard.edu
Hiroyuki
H
Nishimura
Jack L
JL
Strominger
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D051184:Desmoglein 3 / Q000097:blood / Q000276:immunology*; D007114:Immunization; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D001323:Autoantibodies; D051184:Desmoglein 3; C495300:Dsg3 protein, mouse; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG