The role of epithelial cells in the initiation and perpetuation of autoimmune lesions: lessons from Sjogren's syndrome (autoimmune epithelitis)

Abstract

Sjögren's syndrome (SS) is a chronic autoimmune disease affecting epithelial tissues. Exocrine glands are the primary target and their functional impairment comes as a result of immune attack of epithelial cells of the affected organs (autoimmune epithelitis). In this interplay, the role of the epithelial cell is pivotal. Extensive data point to an intrinsically activated status. Moreover, the epithelial cells possess all the features needed in order to act as non-professional antigen presenting cells. Through apoptosis and exosomes release endocellular antigens contributing to tolerance breakdown. In addition, produce cytokines and chemokines that recruit lymphocytes in the immunopathogenic lesion. Herein, we review all the aforementioned aspects of the epithelial activity that lead to the perpetuation of the lesion as well as the probable viral factors for the intrinsic activation. Finally, we propose a model for SS pathogenesis that integrates the knowledge accumulated during the last decade.