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

Zili Zhang, Wenwei Zhong, Doran Spencer, Hong Chen, Huiying Lu, Tatsushi Kawaguchi, James (Jim) Rosenbaum

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)79-91
Number of pages13
JournalCytokine
Volume46
Issue number1
DOIs
StatePublished - Apr 2009

Fingerprint

Interleukin-17
Uveitis
Ovalbumin
Neutrophils
Inflammation
T-cells
T-Lymphocytes
Enzyme-Linked Immunospot Assay
Th17 Cells
Intravitreal Injections
Lymphocytes
Antibodies
T-Lymphocyte Subsets
Chemotaxis
Chemokines
Infiltration
Real-Time Polymerase Chain Reaction
Leukocytes
Cytokines

Keywords

  • Inflammation
  • Interleukin-17
  • Uveitis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

Cite this

Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice. / Zhang, Zili; Zhong, Wenwei; Spencer, Doran; Chen, Hong; Lu, Huiying; Kawaguchi, Tatsushi; Rosenbaum, James (Jim).

In: Cytokine, Vol. 46, No. 1, 04.2009, p. 79-91.

Research output: Contribution to journalArticle

Zhang, Zili ; Zhong, Wenwei ; Spencer, Doran ; Chen, Hong ; Lu, Huiying ; Kawaguchi, Tatsushi ; Rosenbaum, James (Jim). / Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice. In: Cytokine. 2009 ; Vol. 46, No. 1. pp. 79-91.
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