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Jing Zhou, Jun-O, Jin, Juan Du, Qing Yu; Innate Immune Signaling Induces IL-7 Production, Early Inflammatory Responses, and Sjögren's-Like Dacryoadenitis in C57BL/6 Mice. Invest. Ophthalmol. Vis. Sci. 2015;56(13):7831-7838. doi: 10.1167/iovs.15-17368.
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Innate immune signaling elicited by polyinosinic-polycytidylic acid (poly I:C) induces IL-7 production and early inflammatory responses in the salivary gland and accelerates the development of Sjögren's syndrome (SS)-like sialadenitis. Whether poly I:C can induce similar responses in the lacrimal gland (LAC) has not been characterized. In this study, we examined the early responses and pathologic changes of the LAC tissue in response to poly I:C treatment.
Poly I:C or recombinant human IL-7 was injected intraperitoneally into C57BL/6 mice, and the LAC was harvested at different time points. Expression of chemokines and cytokines in the LAC was measured by RT-PCR, immunofluorescence staining, and immunohistochemistry. Leukocytic infiltration and caspase-3 activation were analyzed by hematoxylin and eosin staining and immunohistochemistry. Serum antinuclear antibody levels were also determined. Tear secretion was measured by phenol red cotton threads.
Administration of poly I:C induced IL-7 gene expression and protein production in the LAC. Poly I:C also induced the expression of CXCR3 ligands, monocyte chemoattractant protein-1, IL-23p19, and TNF-α in the LAC in an IL-7–dependent fashion. Similarly to poly I:C, administration of exogenous IL-7 also up-regulated these proinflammatory mediators. Furthermore, repeated administration of poly I:C to C57BL/6 mice over an 8-day period caused leukocytic infiltration and caspase-3 activation in the LAC, antinuclear antibody production, and impaired tear secretion.
Poly I:C induces IL-7 production, early inflammatory responses, and characteristic pathologies of SS-like dacryoadenitis in non–autoimmune-prone C57BL/6 mice. These findings provide new evidence that viral infection-elicited innate immune signaling may be one of the early triggers of SS-like dacryoadenitis.
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