The role of epithelial cells in the immunopathogenesis of Sjögren's syndrome.

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by dysfunction of the affected exocrine glands. Lymphocytic infiltration within the inflamed glands and aberrant B cell hyperactivation are the two salient pathological features in SS. Increasing evidence indicates that salivary gland (SG) epithelial cells act as a key regulator in the pathogenesis of SS, as revealed by the dysregulated innate immune signaling pathways in SG epithelium and increased expression of various proinflammatory molecules as well as their interaction with immune cells. In addition, SG epithelial cells can regulate adaptive immune responses as non-professional antigen-presenting cells and promote the activation and differentiation of infiltrated immune cells. Moreover, the local inflammatory milieu can modulate the survival of SG epithelial cells, leading to enhanced apoptosis and pyroptosis with the release of intracellular autoantigens, which further contributes to SG autoimmune inflammation and tissue destruction in SS. Herein, we reviewed recent advances in elucidating the role of SG epithelial cells in the pathogenesis of SS, which may provide rationales for potential therapeutic targeting of SG epithelial cells to alleviate SG dysfunction alongside treatments with immunosuppressive reagents in SS.