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.
Nishimura
Hiroyuki
H
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.jlstrom@fas.harvard.edu
Strominger
Jack L
JL
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