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Yosuke Asada, Susumu Nakae, Kanji Hori, Jobu Sugita, Nobuyuki Ebihara, Akira Murakami, Akira Matsuda; The roles of epithelial cell derived type 2 initiating cytokines in experimental allergic conjunctivitisThe roles of epithelial cell derived type 2 initiating cytokines in experimental allergic conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4880.
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© ARVO (1962-2015); The Authors (2016-present)
To clarify the possible involvements of type 2 initiating cytokines, interleukin (IL)-25, IL-33, thymic stromal lymphopoietin (TSLP) for the pathophysiology of allergic conjunctivitis using ragweed (RW)-induced experimental allergic conjunctivitis (EAC).
IL-25-/-, IL-33-/-, TSLP receptor (TSLPR) -/- and congenic BALB/C wild type mice were sensitized with ragweed (RW) in alum, and then challenged 4 times using RW eye drops. Clinical score was evaluated at 20 minutes after the last eye drop challenge. The conjunctival tissue was collected for histological analyses and for cytokine expression analysis using real time PCR at 24 hours after the last eye drop challenge.
Significant reduction for the clinical scores and the numbers of infiltrating eosinophils was observed in the RW-induced EAC models using IL-33-/- mice. There was no significant difference of the numbers of infiltrating eosinophils of the RW-EAC models among IL-25-/-, TSLPR-/- and the wild-type mice. The mean numbers of eosinophil per one slide were 17.2 ±1.4 in IL-33-/- mice, 72.0 ± 4.9 in IL-25-/- mice, 79.4 ± 15.3 in TSLPR-/- mice, and 79.3 ± 5.3 in the wild type mice. Il4 mRNA, il13 mRNA and ccl5 mRNA expression was significantly higher in the conjunctivae of RW-EAC models using wild type mice compared to those of IL-33-/- mice. Immunoshistochemical staining using mouse basophil marker mcp8 showed significant reduction of the basophil numbers in the RW-EAC models using IL-33-/- mice (1.25 ± 1.8 per one slides) compared to those of the wild type mice (7.9 ± 5.3).
IL-33 plays essential roles for eosinophil infiltration and the expression of Th2-type cytokines in RW-EAC models. Significant reduction of basophils, which is known as an abundant source of IL-4, may also contribute to the attenuated inflammatory responses in IL-33-/- mice.
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