Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice

Abstract

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.

Activation of OX40 Augments Th17 Cytokine Expression and Antigen-Specific Uveitis

“…Our previous study showed that OVA stimulation up-regulated IL-1␤ and IL-6 transcription in the DO11.10 mice. 9 This may explain how OVA challenge alone can induce IL-17 production in DO11.10 lymphocytes as observed in the current study.…”

“…The OVA-induced uveitis is CD4 ϩ T cell dependent and mainly mediated by IL-17. 9 Since activated T cells express OX40, we investigated OX40 induction in this T cell-dependent uveitis model. DO11.10 mice were intravitreally challenged with 100 g OVA or bovine serum albumin as a control.…”

“…6 In parallel with the observation in human patients, CD4 ϩ and other lymphocytes mediate many animal models of uveitis such as experimental autoimmune uveitis (EAU) and the antigen-specific DO11.10 uveitis model. [7][8][9] These models greatly advance our understanding of the adaptive immune response in ocular inflammation.…”

Prolonged ovalbumin challenge facilitates Th17 polarization in sensitized mice

“…Previous studies found that OVA administration through epicutaneous sensitization or intravitreal injection to the vitreous chamber of the eye could induce a Th17-mediated inflammatory response in vivo [35,36]. The results of our study indicated that with intraperitoneal injection sensitization and prolonged exposure to aerosolized OVA, a Th17-polarized environment could also be created.…”

Systemic augmentation of αB-crystallin provides therapeutic benefit twelve hours post-stroke onset via immune modulation

“…Moreover, these γδ-T cells were producing IL-17 ( Fig. 2G), causing damage rather than tolerance as suggested previously (7,(17)(18)(19)(20).…”