IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease

BackgroundVogt-Koyanagi-Harada (VKH) disease is a systemic refractory autoimmune disease. IL-23 has been thought to play a critical role in autoimmune disease through inducing the development of IL-17–producing CD4+ T cells.ObjectiveTo investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in patients with VKH disease.MethodsBlood samples were taken from 25 patients with VKH disease and 16 healthy controls. Peripheral blood mononuclear cells (PBMCs) were subjected to analysis of IL-23p19 mRNA and IL-23 protein expression using RT-PCR and ELISA, respectively. The IL-17 levels in the supernatants of PBMCs and CD4+ T cells cultured in the absence or presence of recombinant (r)IL-23, rIL-12, or anti–IFN-γ were determined by ELISA.ResultsThe patients with VKH disease with active uveitis showed an elevated level of IL-23p19 mRNA in PBMCs, higher IL-23 in the serum and supernatants of PBMCs, and increased production of IL-17 by polyclonally stimulated PBMCs and CD4+ T cells. Recombinant IL-23 significantly enhanced IL-17 production, whereas rIL-12 and IFN-γ inhibited IL-17 production. More importantly, IL-17 production was significantly increased in patients with active uveitis in the presence of rIL-23. Both rIL-23 and rIL-12 enhanced IFN-γ production.ConclusionThe results suggest that IL-23–stimulated production of IL-17 by CD4+ T cells may be responsible for the development of uveitis seen in patients with VKH disease.Clinical implicationsThis study provides a new insight into the mechanism involved in the development of VKH disease.