Ocular Behcet's disease is associated with aberrant methylation of interferon regulatory factor 8 (IRF8) in monocyte-derived dendritic cells

Yiguo Qiu, Yunyun Zhu, Hongsong Yu, Shenglan Yi, Wencheng Su, Qingfeng Cao, Gangxiang Yuan, Aize Kijlstra, Peizeng Yang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Web of Science)

Abstract

Aberrant methylation of interferon regulatory factor 8 (IRF8) has been noted in various tumors. IRF8 has also been reported to be involved in many autoimmune diseases, including Behcet's disease (BD). However, the methylation status of IRF8 in BD has not been reported. To address this issue, we investigated whether the degree of methylation of IRF8 in dendritic cells (DCs) plays a role in the development of BD. We found a lower mRNA expression and a higher methylation level of IRF8 in active ocular BD patients as compared to normal subjects and inactive patients. Treatment with a demethylation agent, 5-Aza-2'-deoxycytidine (DAC) resulted in an increase of mRNA expression and a reduction of the IRF8 methylation level. It also down-regulated the expression of the co-stimulatory molecules CD86, CD80, CD40, and reduced the production of IL-6, IL-1 beta, IL-23 and IL-12. An inhibition of Th1/Th17 responses was observed as evidenced by a decreased production of IFN-., IL-17, and a reduction of IFN-gamma/IL-17-producing CD4(+) T cells following treatment with DAC. This study shows that active ocular BD patients have an aberrant IRF8 methylation status. These findings suggest that epigenetic control of IRF8 expression may offer a future target in the treatment of ocular BD.

Original languageEnglish
Pages (from-to)51277-51287
Number of pages11
JournalOncotarget
Volume8
Issue number31
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • DNA methylation
  • interferon regulatory factor 8
  • Behcet's disease
  • dendritic cells
  • WIDE DNA METHYLATION
  • NAIVE CD4+T CELLS
  • TRANSCRIPTION FACTOR
  • ACTIVE UVEITIS
  • HAN CHINESE
  • ACTIVATION
  • IMMUNITY
  • EXPRESSION
  • FAMILY
  • SUSCEPTIBILITY

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