Purchase this article with an account.
Z. Zhang, W. Zhong, D. Spencer, J. T. Rosenbaum; Interleukin-17 Mediates Ovalbumin-Induced Uveitis in DO11.10 Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2533.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
T cell-mediated uveitis is strongly associated with systemic inflammatory disorders including inflammatory bowel disease, sarcoidosis, ankylosing spondylitis, and juvenile idiopathic arthritis. Recent studies have discovered a novel subpopulation of T cells, called Th17 cells. These cells have a characteristic of producing interleukin (IL)-17, and are highly pathogenic. In this study, we employed DO11.10 mice to investigate the role of IL-17 in the pathogenesis of uveitis. CD4+ T cells in DO11.10 mice are genetically engineered to react with ovalbumin (OVA).
First, DO11.10 splenocytes were isolated to assess their response to OVA in vitro. Next, we examined whether OVA stimulation could elicit local inflammation and induce IL-17 in vivo. Uveitis was induced by intravitreal injection of OVA. At 24 hours after OVA injection, ocular inflammation was evaluated by intravital microscopy. Then, the mice were sacrificed and the eyes were harvested for various analyses.
ELISPOT assay revealed that in vitro OVA challenge significantly induced IL-17 production. Furthermore, OVA elicited marked neutrophil-predominant inflammatory cell infiltration in the eyes. This leukocyte influx appeared to be mediated by CD4+ lymphocytes as evidenced by the fact that depletion of CD4+ cells by GK1.5 antibody significantly inhibited the ocular inflammation. Compared to control mice receiving vehicle alone, real time-PCR showed that OVA treatment induced an array of IL-17-related gene expression. Moreover, intraocular injection of anti-IL-17 antibody markedly reduced OVA-mediated inflammatory cell infiltration in the eyes. Finally, anti-IL-17 antibody attenuated ocular expression of CXCL2 and CXCL5, two well documented neutrophil chemotactic cytokines.
These results indicate that we have established a uveitis model to study the contribution of Th17 cells. Furthermore, our study suggests that IL-17 is implicated in the pathogenesis of T cell-mediated uveitis in part through neutrophil chemotaxis as its downstream effect.
This PDF is available to Subscribers Only