Activation of AIM2 inflammasome in salivary gland epithelial cells of patients with primary Sjögren’s syndrome

Abstract

Abstract Sjögren’s syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. Although an association between inflammasome activation in peripheral blood cells and disease activity of SS has been reported, little is known about inflammasome activation in exocrine glands and its underlying mechanisms. We investigated the levels of AIM2, ASC, caspase-1, IL-1β, and IL-18 in salivary gland tissues and saliva from SS patients. We found that AIM2, ASC, Caspase-1, and IL-18 were increased in the saliva from primary SS patients compared with healthy and sicca controls. Numbers of AIM2-ASC speck also were elevated in the salivary gland epithelial cells of SS patients. The expression of caspase-1 correlated with type I interferon (IFN) signature gene expressions in the minor salivary glands (MSG) of SS patients, and was increased by type I IFN stimulation in salivary gland epithelial cells (SGECs). The AIM2 inflammasome was activated in SGECs after stimulation by the AIM2 ligand, poly(dA:dT). In addition, type I IFN accelerated AIM2 inflammasome activation as determined by the increased expression of caspase-1 in SGECs. In conclusion, the AIM2 inflammasome activation is increased in the SGECs of SS patients, and therefore should be considered an important pathogenic mediator of SS disease.