Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice.
T cell-mediated uveitis is strongly associated with many systemic inflammatory disorders. Th17 cells are a novel T cell subset characterized by production of interleukin (IL)-17. In this study, we used 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). IL-17 expression was determined by real-time PCR and ELISPOT. Uveitis was induced by intravitreal injection of OVA, and ocular inflammation was evaluated by intravital microscopy. OVA challenge significantly induced IL-17 production by DO11.10 splenocytes in vitro. Next, we examined whether OVA challenge could elicit local inflammation and induce IL-17 in vivo. OVA elicited marked neutrophil-predominant inflammatory cell infiltration in the eyes. This leukocyte influx was mediated by CD4(+) lymphocytes as evidenced by significant inhibition of the ocular inflammation by CD4+ depleting antibody. Compared to control mice, OVA treatment induced IL-17 expression. Moreover, anti-IL-17 antibody markedly reduced OVA-mediated ocular inflammation. Finally, the neutralization of IL-17 attenuated ocular expression of CXCL2 and CXCL5, two cytokines which are chemotactic for neutrophils. Our study suggests that IL-17 is implicated in the pathogenesis of this T cell-mediated model of uveitis in part through neutrophil chemotaxis as a downstream effect of IL-17.
Zhang
Zili
Z
Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA. zhangzi@ohsu.edu
Zhong
Wenwei
W
Spencer
Doran
D
Chen
Hong
H
Lu
Huiying
H
Kawaguchi
Tatsushi
T
Rosenbaum
James T
JT
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005123:Eye / Q000382:microbiology; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008853:Microscopy / Q000379:methods; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014605:Uveitis / Q000276:immunology / Q000378:metabolism*
D054365:Chemokine CXCL5; C094739:Cxcl5 protein, mouse; D020381:Interleukin-17; D010047:Ovalbumin