Primary Sjögren's syndrome (SS) is characterized by chronic periductal inflammatory infiltrates in the salivary glands. Several previous studies have indicated that the ductal epithelia of SS patients play a pro-inflammatory role and manifest an intrinsically activated status, as demonstrated in cultured non-neoplastic ductal salivary gland epithelial cell (SGEC) lines. Herein, we investigated the activation of inflammasomes in the salivary epithelia of SS patients and non-SS controls, using salivary biopsy tissues and SGEC lines. The ductal epithelial cells of SS patients were found to display significant activation of the AIM2 (absent in melanoma-2) inflammasome. Such activation occurred in a cell-autonomous manner, as it was illustrated by the constitutively high expression of AIM2 activation-related genes, the presence of cytoplasmic ASC specks and the increased spontaneous IL-1β production observed in patients' SGEC lines. Since AIM2 activation is known to occur in response to cytoplasmic DNA, we further searched for the presence of undegraded extranuclear DNA in the SGEC lines and SG tissues of patients and controls. This investigation revealed marked cytoplasmic accumulations of damaged genomic DNA that co-localized with AIM2 in the specimens of SS patients (but not controls). The SGEC lines and the ductal tissues of SS patients were also found to manifest impaired DNase1 expression and activity, which possibly denotes defective cytoplasmic DNA degradation in patients' cells and AIM2 triggering thereof. In corroboration, DNase1-silencing in normal SGEC was shown to lead to high AIM2-related gene expression and IL-1β production. Our findings indicate that the cell-intrinsic activation status of ductal epithelia in SS patients owes to persistent epithelial AIM2 activation by aberrant cytoplasmic DNA build-up.

原发性干燥综合征（SS）的特征是唾液腺中慢性导管周围炎性浸润。先前的一些研究表明，SS患者的导管上皮发挥促炎作用，并表现出内在的激活状态，这在培养的非肿瘤性导管唾液腺上皮细胞（SGEC）系中得到了证实。在这里，我们调查了唾液活检组织和SGEC线的SS患者和非SS控件的唾液上皮中炎性小体的激活。发现SS患者的导管上皮细胞显示出AIM2（黑色素瘤2中不存在）炎症小体的显着激活。这种激活以细胞自主方式发生，如AIM2激活相关基因的组成型高表达所证明的那样，在患者的SGEC细胞系中观察到细胞质ASC斑点的存在和自发IL-1β产生的增加。由于已知AIM2激活是响应细胞质DNA发生的，因此我们进一步搜索了患者和对照SGEC系和SG组织中是否存在未降解的核外DNA。这项研究揭示了SS患者标本中与AIM2共定位的受损基因组DNA的明显细胞质积累（但没有对照）。还发现SS患者的SGEC细胞系和导管组织显示出DNase1表达和活性受损，这可能表示患者细胞中的胞浆DNA降解缺陷以及其AIM2触发。有确凿的证据表明，正常SGEC中的DNase1沉默会导致高AIM2相关基因表达和IL-1β产生。