Scurfy Mice Develop Features of Connective Tissue Disease Overlap Syndrome and Mixed Connective Tissue Disease in the Absence of Regulatory T Cells

Scurfy Mice Develop Features of Connective Tissue Disease Overlap Syndrome and Mixed Connective Tissue Disease in the Absence of Regulatory T Cells Osman K. Yilmaz1, Stefanie Haeberle1, Meifeng Zhang1, Marvin J. Fritzler2, Alexander H. Enk1 and Eva N. Hadaschik1,3* 1Department of Dermatology, University of Heidelberg, Heidelberg, Germany 2Mitogen Advanced Diagnostics Laboratory, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada 3Department of Dermatology, University Hospital of Essen, Essen, Germany Due to a missense mutation in the Foxp3 gene, scurfy mice are deficient in functional regulatory T cells (Treg). The consequent loss of peripheral tolerance manifests itself by fatal autoimmune mediated multi-organ disease. Previous studies have outlined the systemic inflammatory disease and demonstrated production of anti-nuclear antibodies (ANA) in scurfy mice. However, specific autoantibody targets remained to be defined. ANA are immunological markers for several connective tissue diseases (CTD) and target a large number of intracellular molecules. Therefore, we examined scurfy sera for the presence of different ANA specificities and further assessed the organ involvement in these animals. Indirect immunofluorescence was used as a screen for ANA in the sera of scurfy mice and dilutions of 1/100 were considered positive. Addressable laser bead immunoassays (ALBIA) were used to detect specific autoantibody targets. Subsequent histological tissue ev...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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