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Eiichi Hasegawa, Takashi Shichita, Yuji Oshima, Atsunobu Takeda, Takeru Yoshimura, Koh-hei Sonoda, Tatsuro Ishibashi, Akihiko Yoshimura; Tcells Promote Experimental Choroidal Neovascularization In An Il-23-independent Manner. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1231.
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Interleukin(IL)-17 is a proinflammatory cytokine associated with autoimmunity and defense against bacteria; it has been implicated in many autoimmune diseases such as psoriasis, rheumatoid arthritis and uveitis. Previously, we demonstrated that IL-17, which is mainly produced by γΔTcells, promotes choroidal neovascularization (CNV) in mouse laser-induced model. Both IL-1β and IL-23 have been reported to be indispensable for IL-17 expression in Th17 cells, γΔTcells and other IL-17 producing cells. Herein we report the expression of IL-1β and IL-23 in laser-treated eyes and their involvement in IL-17 expression by γΔTcells.
Adult wild-type C57BL/6J mice and IL-23p19 knockout (KO) mice received laser photocoagulation (wave length=532 nm, 0.1s, spot size=75 µm, power=200mW) to induce CNV. Cytokine expression in laser-treated eyes was evaluated by quantitative real-time PCR at multiple time points. To analyze CNV area, mice were perfused with fluorescein-lableled dextran on day 7. Eyes were harvested and fixed, and the choroid-scleral flatmount was subjected to image analysis. FACS-sorted γΔTcells were cultured with or without IL-1β or IL-23. After 48hrs, IL-17 expression in the culture supernatant was measured by ELISA.
Both CNV area and IL-17 mRNA expression were comparable between eyes from wild-type mice and IL-23p19KO mice. However, eyes from IL-23p19 KO mice had significantly higher levels of IL-1β mRNA expression compared to eyes from wild-type mice. IL-17 production by cultured γΔTcells was enhanced by both IL-1β and IL-23, but it was also enhanced by IL-1β alone.
These results suggest that even without IL-23, IL-1β alone is sufficient to induce IL-17 production by γΔTcells in the laser-treated eye.
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