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D. Luger, P. B. Silver, D. Cua, Y. Iwakura, E. P. Bowman, C.-C. Chan, R. R. Caspi; Il-23 and Il-17 in Pathogenesis of Experimental Ocular Autoimmunity: Requirement for Il-23 May Extand Beyond Its Role in Sustaining the Il-17 Effector Response. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1097.
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© ARVO (1962-2015); The Authors (2016-present)
Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in humans. The proinflammatory cytokine IL-23 promotes the autopathogenic Th17 population, characterized by the production of IL-17, IL-6, and TNF. In the present study we examined the role of the IL-23/IL-17 pathway in EAU.
We used IL-23p19, IL-12p35, IL-12p40, IFN-g and IL-17 KO mice immunized with the uveitogenic antigen IRBP. Alternatively, we treated EAU-challenged wild type mice with anti IL-23p19 or anti IL-17 Ab throughout the disease course (prevention), or only during the effector phase (reversal).
IL-23p19 and IL-12p40 KO were resistant to EAU, showing reduced Ag specific DTH, IL-2, IFN-g, IL-17, IL-1b, IL-6 and IL-5. In contrast, IL-12p35 and IFN-g KO mice developed exacerbated EAU, DTH and IL-17 responses. Treatment with anti-IL-23p19 protected from EAU and reduced immunological responses, but was unable to reverse disease, indicating that EAU is dependent on early availability of IL-23. In contrast, anti IL-17 prevented and reversed EAU. Interestingly, severe EAU was induced with a T cell line producing IFN-g and no IL-17, suggesting that an IFN-g producing effector phenotype can be sufficient to induce the full picture of EAU.
These data raise the possibility that the nonredundant need for IL-23 in EAU may extend beyond its role in promoting the Th17 effector response and point to IL-23 and IL-17 as new therapeutic targets for uveitis.
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