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Rosa M. Corrales, Flavia Pelegrino, Eugene Volpe, De-Quan Li, Stephen C. Pflugfelder, Cintia S. De Paiva; IL-17 Deletion Accelerates Onset and Severity of Dacryoadenitis in CD25KO mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6184.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of IL-17 on the onset and severity of dacryoadenitis in the CD25 knock-out (KO) mouse model of Sjögren’s syndrome.
CD25/IL17 double KO (17DKO) mice were created by crossbreeding CD25KO and IL-17KO and they were compared to both parental strains. Mice were used at 4, 8, 12, 16 weeks (W). Total cell infiltrates were visualized in histology sections stained for H&E and quantified as % infiltration in digital images. CD4, CD8 and B cell infiltration were visualized by immunohistochemistry in paraffin-embbeded sections and quantified by flow cytometry analysis. LG function was evaluated by measuring EGF concentration in tears collected at the same time points.
Parental strain CD25KO LG had significant lymphocytic infiltration (37.32±15.38%) at 4W of age, which rapidly progressed to 89.18±8.07% at 8 and 12W (93.47±6.77), reaching 93.47±9.46% at 16W of age. Total disarragement of normal lacrimal gland architecture was observed from 12W of age and complete atrophy at 16W, including periductal fibrosis and ductal proliferation. Lymphocytic infiltration in young (4W) 17DKO mice was significantly higher (76.22±14.27%) than parental strains IL-17KO and CD25KO mice at similar age (12.76±5.77% and 37.32±15.38%, respectively, P<0.001) and reached 95.30±3.08% at 8W of age and remained elevated until 16W of age. IL-17KO mice had some lymphocytic infiltrates (12.76±5.77, 15.96±13.14, 30.44±8.08 and 16.03±13.74 at 4, 8 12 and 16W respectively), but retained normal acini and normal architecture in all ages evaluated. Immunohistochemistry in LG demonstrated that the infiltrates were a mix of CD4, CD8 and CD19 positive (+) cells in all strains. Flow cytometry analysis showed an increase in CD4+, CD8+T and B cells with aging in 17DKO LG and this strain had significantly higher numbers of positive cells than both parental strains IL17KO and CD25KO at any age. Tear EGF production in parental strain IL-17KO was significantly higher than 17DKO and CD25KO strains and it was in normal range at all ages. CD25KO mice had normal EGF levels only at 4W of age, while 17DKO mice had barely detectable tear EGF levels at any age. Tear EGF concentration inversely correlated with degree of LG CD4 and CD8+T cell infiltration (R2=0.86, R2=0.93, P<0.005 and P=0.0006, respectively).
The deletion of IL-17 in CD25KO mice strain accelerates the onset and severity of dacryoadenitis. The decrease in LG function correlated with the increased presence of T cells. Taken together, our findings suggest that IL-17A may have a protective role in early stages of the disease.
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