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Genomic DNA activates the AIM2 inflammasome and STING pathways to induce inflammation in lacrimal gland myoepithelial cells.
- Source :
-
The ocular surface [Ocul Surf] 2023 Oct; Vol. 30, pp. 263-275. Date of Electronic Publication: 2023 Sep 26. - Publication Year :
- 2023
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Abstract
- Purpose: Primary Sjögren's syndrome (pSS) is an autoimmune disease that mainly attacks the lacrimal glands causing severe aqueous-deficient dry eye. Clinical evidence indicates the DNA sensing mechanism in the pathogenesis of pSS. The purpose of the present study is to determine the pro-inflammatory effect of self-genomic DNA (gDNA) on myoepithelial cells (MECs), which along with acinar and ductal cells is a major cell type of the lacrimal gland.<br />Method: MECs primary culture was acquired from female C57BL6J mice. Genomic DNA was extracted from the spleen of the same animal. The MECs were challenged with self-gDNA. The cytokine secretion was detected using supernatant by enzyme-linked immunosorbent assay (ELISA). The activation of inflammasomes was determined using FAM-FLICA. Cryosections of NOD.B10.H2 <superscript>b</superscript> mouse model of pSS were obtained for immunofluorescence microscopy (IF), with Balb/C as control.<br />Result: Treatment with gDNA activated AIM2 inflammasome assembly and function, leading to secretion of interleukin (IL)-1β and IL-18 in MECs. The stimulation of IL-1β secretion by gDNA appeared to be solely at the post-translational level, whereas IL-18 secretion was a combination of increased protein synthesis and post-translational modification. Genomic DNA also induced the activation of STimulators of INterferon Genes (STING), which correlated to the activation of STING in the lacrimal gland from the NOD.B10.H2 <superscript>b</superscript> mouse. STING activation led to the secretion of IFN-β via Nuclear Factor-κB (NF-κB). The IFN-β further enhances the secretion of IL-1β. The contractility of MECs was disabled by treatment with gDNA or poly AnT, independent of the level of intracellular [Ca <superscript>2+</superscript> ].<br />Conclusion: Self-gDNA induces a proinflammatory response in lacrimal gland MECs by activating both the AIM2 inflammasome and STING and thus may contribute to the pathogenesis of pSS.<br />Competing Interests: Declaration of competing interest None.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1937-5913
- Volume :
- 30
- Database :
- MEDLINE
- Journal :
- The ocular surface
- Publication Type :
- Academic Journal
- Accession number :
- 37769964
- Full Text :
- https://doi.org/10.1016/j.jtos.2023.09.012