Upregulation of T-bet expression in peripheral blood mononuclear cells during Vogt-Koyanagi-Harada disease

Abstract

Aim: To test the hypothesis that T-bet expression is altered in patients with Vogt-Koyanagi-Harada (VKH) disease. Methods: Peripheral blood was withdrawn from 16 VKH patients before and after immunosuppressive treatment and from 16 healthy individuals. IFN-c, IL-2, and IL-4 in the serum and the supernatants of peripheral blood mononuclear cells (PBMC) cultured with or without phytohaemagglutinin (PHA) were measured by ELISA. T-bet mRNA and protein expression in PBMC cultured with or without PHA was detected by RT-PCR and western blot, respectively. Results: The level of IFN-c, but not IL-2 and IL-4, was significantly higher in the supernatants of stimulated PBMC in patients than in controls. A significantly increased T-bet mRNA was found in VKH patients during an active uveitis episode, but not in quiescent patients, compared to controls. T-bet protein was detectable in VKH patients during an active uveitis episode, but not in quiescent patients nor in the healthy controls. Stimulation of PBMC with PHA resulted in a marked upregulation of T-bet mRNA and protein expression for both patients and controls with no significant difference between the two groups. Conclusions: Upregulation of T-bet may be associated with the development of a Th1 mediated immune response in VKH disease.

Promoter Hypermethylation of GATA3, IL-4, and TGF-β Confers Susceptibility to Vogt-Koyanagi-Harada Disease in Han Chinese

“…[7][8][9] Various studies have found that cytokines are crucial in the occurrence and development of VKH disease. 7,10,11 Upregulated expression of IFN-c, IL-17, TBX21, and RORct in peripheral blood mononuclear cells (PBMCs) was detected in active VKH patients, 10,[12][13][14] suggesting that Th1 and Th17 lymphocytes are associated with this disease.…”

Immune mechanisms of intraocular inflammation

“…Despite this, most human data confirm a predominance of activated CD4 + T cells orchestrating the pathogenesis of noninfectious uveitis [96,[100][101][102]. Corroborating the animal data discussed earlier, studies in patients with intermediate uveitis, Behçet's uveitis and VKH have also demonstrated a predominance of Th1 cells expressing high levels of IL-2, IFN-g, IL-12 and the transcription factor Tbet [102][103][104][105][106][107]. Further indirect evidence for the CD4 + Th1 drive is the suppression of IFN-g and IL-12 production observed during clinical improvement of active uveitis [108,109].…”

T-bet expression in the iris and spleen parallels disease expression during endotoxin-induced uveitis

“…Our previous study revealed that T-bet expression at the mRNA and protein levels is upregulated in Behcet's and Vogt-Koyanagi-Harada patients with active intraocular inflammation [8,9]. Salvati et al [25] found that T-bet expression was increased in the inflamed mucosa of patients with celiac disease.…”