Insight into pathogenesis of Sj?gren's syndrome: Dissection on autoimmune infiltrates and epithelial cells

摘要

Abstract Sj?gren's syndrome (SS) is a chronic autoimmune disease with broad clinical spectrum, extending from benign exocrinopathy to severe systemic disease and lymphoma development. The glandular and extraglandular dysfunction of SS is associated with lymphocytic infiltrates that invade the epithelial structures of affected organs. The in-depth study of autoimmune lesions in the minor salivary glands (MSG), which are the major target-organ of SS responses, revealed that the lymphocytic infiltrates vary in severity and composition among SS-patients, are full-blown at diagnosis and remain unchanged thereafter. Although the pathogenetic pathways underlying SS have not yet elucidated, it is well-established that glandular epithelial cells are central regulators of local autoimmune responses. Moreover, chronic inflammation affects epithelial function and phenotype, which strengthens or weakens their immunoregulatory/secretory function, leading to deterioration of autoimmune phenomena. Herein, the current findings regarding the autoimmune lesions, the role of epithelial cells and their interaction with infiltrating lymphocytic cells are discussed. Highlights ? The autoimmune infiltrates of minor salivary glands (MSG) of SS patients vary in grade and cellular composition ? The grade and cellular composition of MSG lesions is full-blown at diagnosis and does not significantly change thereafter ? Salivary gland epithelial cells (SGEC) are major regulators of local inflammatory responses ? SGEC of SS patients are intrinsically activated ? The chronic inflammation further modifies SGEC immune-regulatory and secretory function creating a vicious cycle