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E. Rahimy, W. J. Farley, J. D. Pitcher, J. Niederkorn, M. E. Stern, D.-Q. Li, S. C. Pflugfelder, C. S. De Paiva; Spontaneous Autoimmune Dacryoadenitis in Aged CD25KO. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4665.
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To investigate age-related changes in function and immunopathology in the lacrimal gland (LG) of IL-2R -/- (CD25KO) mice, a previously reported animal model of Sjögren’s Syndrome.
The extraorbital lacrimal glands of C57BL/6 (wild-type) and CD25KO mice were obtained at 8, 12, and 16 weeks of age. Frozen sections of the glands were immunohistochemically stained for T cell markers (CD4, CD8a), monocytes (CD11b), dendritic cells (CD11c), lymphocytes (CD45, CD45RA), and intraepithelial lymphocytes (γΔTCR, CD103). Lacrimal gland function was assessed by measuring peroxidase secretion in tears and by measuring EGF expression by real time PCR. T helper (Th)-1, 2 and 17 associated cytokine expression was evaluated by real time PCR.
8-week old CD25KO mice demonstrated significantly increased CD4+ and CD8+ T cell , CD11b, CD11c, CD45, CD45RA, γΔTCR, and CD103 infiltration of the lacrimal gland when compared to LG wild-type. There was a progressive increase in these cells up to 12 weeks of age, followed by a decrease at 16 weeks, in both strains. Peroxidase secretion in tears peaked at 8-weeks and showed a significant decrease with aging in C57BL/6 mice. No peroxidase secretion was detected in CD25KO mice at any age. Expression of EGF mRNA in LG decreased at 12 weeks of C57BL/6 mice, compared to younger mice and it was barely detected in CD25KO mice at all ages. Young CD25KO LG had higher Th-17 (IL-23R, TGF-β1, IL-17A, CCL20) and Th-1 associated cytokine transcripts (IFN-γ, t-bet, IL-12, IL-2, IL-12rB1, IL-18, IL-18R) than young wild-type. Aging induced a significant decrease in IL-17A and CCL20 in CD25KO LG, compared to a significant increase in IL-17A, TGF-β1&2, IL-23R, CCL20 and IFN-γ in C57BL/6 LG.
Autoimmune infiltration in the lacrimal gland of CD25KO mice was observed as early as 8 weeks of age. This infiltration was accompanied by a loss of lacrimal gland function. Aged C57BL/6 mice showed a mix of Th-17 and Th-1 inflammation, whereas aging in CD25KO mice suggested a switch from Th-17 to Th-1 inflammation.
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