Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease

Yiguo Qiu, Hongsong Yu, Yunyun Zhu, Zi Ye, Jing Deng, Wencheng Su, Qingfeng Cao, Gangxiang Yuan, Aize Kijlstra, Peizeng Yang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

Abstract

Aberrant methylation change of IRF8 confers risk to various tumors, and abnormal expression of IRF8 is involved in many autoimmune diseases, including ocular Behcet's disease. However, whether the methylation change of IRF8 is associated with Vogt-Koyanagi-Harada (VKH) disease remains unknown. In the present study, we found a decreased IRF8 mRNA expression in association with a higher methylation level in monocyte-derived dendritic cells (DCs) from active VKH patients compared with the normal and inactive subjects. DCs incubated with cyclosporin a (CsA) or dexamethasone (DEX) showed a lower methylation and higher mRNA expression of IRF8 in active VKH patients. A demethylation reagent, 5-Aza-2'-deoxycytidine (DAC) showed a notable demethylation effect as evidenced by increasing the mRNA expression and reducing the methylation level of IRF8. It also suppressed the Th1 and Th17 responses through down-regulating the expression of co-stimulatory molecules (CD86, CD80, CD40), and reducing the production of pro-inflammatory cytokines (IL-6, IL-1 beta, IL-23, IL-12) produced by DCs. These findings shows that hypermethylation of IRF8 in DCs confers risk to VKH disease. Demethylation of IRF8 may offer a novel therapeutic strategy protect against VKH disease.

Original languageEnglish
Article number1007
Number of pages10
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 21 Apr 2017

Keywords

  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • SEQUENCE-BINDING-PROTEIN
  • NF-KAPPA-B
  • DENDRITIC CELLS
  • TRANSCRIPTION FACTOR
  • BEHCETS-DISEASE
  • SUSCEPTIBILITY LOCI
  • AUTOIMMUNE-DISEASES
  • MULTIPLE-SCLEROSIS
  • IMMUNE-RESPONSES

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