Local suppression of IL-21 in submandibular glands retards the development of Sjogren's syndrome in non-obese diabetic mice

BACKGROUND: The aim of this study was to verify the validity of IL-21 local suppression in submandibular glands of preventing the development of Sjogrens syndrome in non-obese diabetic (NOD) mice and figure out the mechanism. METHODS: IL-21 levels in submandibular glands were suppressed by ductal cannulation of IL-21 shRNA lentivirus. Then, saliva flow rates (SFR) and histopathologic changes of submandibular glands were measured to assess the severity of disease development. Real-time PCR, flow cytometry, and immunohistochemistry were used to detect the changes of T helper cells and related cytokines. RESULTS: The reduction in SFRs in NOD mice was significantly alleviated from 9 to 17 weeks of age along with the suppression of IL-21 in submandibular glands. Lymphocytic infiltration was also milder than control NOD mice. Moreover, the lower level of IL-21 led to the down-regulation of follicular helper T (Tfh) cells. CONCLUSIONS: Local suppression of IL-21 in submandibular glands could retard the development of Sjogrens syndrome in NOD mice. IL-21 might contribute to the development of B-cell disorder in Sjogrens syndrome via Tfh cells pathway. J Oral Pathol Med (2012) 41: 728-735