Background/Purpose: Sjögren’s syndrome (SS), an autoimmune disease that targets the salivary and lacrimal glands which causes dry eyes (xerophthalmia) and dry mouth (xerostomia) phenotypes. In the salivary gland, the reduction or complete loss of saliva secretion has been attributed to acinar cell dysfunction. Although the underlying mechanisms are unclear, more than 50% of SS patients display high activity of type I and II interferon (IFN) responses.

Methods: We established primary human salivary gland epithelial cell culture (phSG) conditions that either retains highly proliferative growth or display differentiated acinar-like phenotype. Whole Transcriptome profiling (RNA-Seq) revealed calcium-regulated and differentially expressed miRNAs.

Results: One of these differentially expressed miRNAs, miR-1248, increases more than 8-fold in phSG cells after calcium switch. Transfection of miR-1248 mimics into phSG cells results in up-regulation of Stat1 (6-fold), Stat2 (3-fold), JAK1 (2.5-fold) and JAK2 (4-fold). Also interferon-stimulated genes (ISG) of MX1, OAS1 and ISG15 were markedly elevated indicating the involvement of miR-1248 in regulation of IFN signaling pathway. Knockdown of IFNAR1/IFNAR2 in miR-1284 mimic-transfected phSG cells showed greatly reduced MX1 induction. IFN-b and -g were detected in culture media in miR-1248 mimic-transfected phSG and primary T cells, respectively, confirmed the production and secretion of these cytokines. Digital PCR assays revealed that the level of endogenous miR-1248 in human salivary glands biopsy from SS patients was higher than that in healthy control.

Conclusion: our data provide a potential underlying mechanism for the elevation of IFN responses regulated by differentially expressed miRNA in Sjögren’s syndrome patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/regulation-of-interferon-signaling-by-a-calcium-induced-mirna-in-primary-human-salivary-gland-epithelial-cells/