Abstract
Sjögren syndrome (SS) is an autoimmune disease characterized by diffuse lymphoid cell infiltrates in the salivary and lacrimal glands, resulting in symptoms of dry mouth and eyes due to insufficient secretion. Although it has been assumed that a combination of immunologic, genetic and environmental factors may play a key role in the development of autoimmune lesions in the salivary and lacrimal glands, little is known about the disease pathogenesis of SS in humans. We have identified the 120 kDa α-fodrin as an important autoantigen in the development of SS in both an animal model and SS patients, but the mechanism of α-fodrin cleavage leading to tissue destruction in SS remains unclear. Tissue-infiltrating CD4+ T cells purified from the salivary glands of a mouse model for SS bear a large proportion of Fas ligand and the salivary gland duct cells possess apoptotic receptor Fas. Anti-Fas antibody-induced apoptotic salivary gland cells result in specific α-fodrin cleavage to the 120 kDa fragment in vitro. Preincubation with a combination of calpain andcas-pase inhibitor peptides could be responsible for inhibition of the 120 kDa α-fodrin cleavage. Thus, an increase in apoptotic protease activities including calpain and caspases may be involved in the progression of α-fodrin proteolysis and tissue destruction in the development of SS.
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Hayashi, Y. (2001). Involvement of Apoptotic Protease Cascade for Tissue Destruction in Sjögren’s Syndrome. In: Górski, A., Krotkiewski, H., Zimecki, M. (eds) Autoimmunity. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0981-2_10
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DOI: https://doi.org/10.1007/978-94-010-0981-2_10
Publisher Name: Springer, Dordrecht
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