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Peizeng Yang, Chaokui Wang, Lichun Tian, Ju Shao, Fuzhen Li, Yuan Tian, Lei Bo, Shengping Hou, Kijlstra Aize; CD4+ T Cells In Vogt-koyanagi-harada Disease Show A Decreased Stimulation Of IL-27 Expression By Dendritic Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6638.
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© ARVO (1962-2015); The Authors (2016-present)
VKH disease is a systemic autoimmune disease. IL-27 has emerged as an important regulator of proinflammatory T cell responses. This study was designed to investigate the pathophysiological role of IL-27 in VKH disease.
Blood samples were taken from 67 patients with VKH disease and 67 healthy controls. PBMCs were subjected to analysis of IL-27 mRNA expression using RT-PCR. The levels of IL-10, IL-17, IL-22 and IFN-γin the CD4+ T cells culture supernatants and the concentration of IL-27 in the serum and supernatants of PBMCs, DCs, DC-T cocultures, or Transwell cultures were assayed by ELISA. CD4+ T cells were cultured with recombinant IL-27 to evaluate its influence of IL-17 expression by these cells. The in vivo and in vitro influence of corticosteroids and Cyclosporin on IL-27 was evaluated in VKH patients. rAAV2.CMV.mIL-27 was subretinally injected into the mice to evaluate its influence on EAU induced by IRBP161-180 clinically and histologically.
The patients with active VKH disease showed a decreased IL-27 mRNA expression and protein expression in association with an increased IL-10, IL-21, IL-17, IFN-γand IL-22 expression. Upregulation of IL-10 and IL-21 by CD4+ T cells, but not cell contact, contributed to the downregulation of IL-27 by DCs in this disease. Recombinant IL-27 significantly inhibited the production of IL-17 by CD4+ T cells. Treatment with corticosteroids and Cyclosporin resolved the intraocular inflammation in association with an upregulation of IL-27 and a downregulation of IL-17. In vitro experiments showed that corticosteroids, but not Cyclosporin, significantly upregulated the expression of IL-27. Subretinal injection of rAAV2.CMV.mIL-27 into the mice significantly ameliorated EAU activity.
CD4+ T cells in VKH disease have a lower stimulatory capacity to induce IL-27 expression by DCs, which in turn leads to an impaired regulation of Th17 response. These results suggests that IL-27 may be potentially used for the treatment of the diseases mediated by upregulated IL-17 response coupled with a downregulated IL-27 expression.
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