Oncotarget

Research Papers:

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 and Peizeng Yang _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:51277-51287. https://doi.org/10.18632/oncotarget.17235

Metrics: HTML 1073 views  |   ?  


Abstract

Yiguo Qiu1, Yunyun Zhu1, Hongsong Yu1, Shenglan Yi1, Wencheng Su1, Qingfeng Cao1, Gangxiang Yuan1, Aize Kijlstra2 and Peizeng Yang1

1The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China

2University Eye Clinic Maastricht, Maastricht, The Netherlands

Correspondence to:

Peizeng Yang, email: peizengycmu@126.com

Keywords: DNA methylation, interferon regulatory factor 8, Behcet’s disease, dendritic cells

Received: February 15, 2017    Accepted: March 28, 2017    Published: April 19, 2017

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-1β, IL-23 and IL-12. An inhibition of Th1/Th17 responses was observed as evidenced by a decreased production of IFN-γ, IL-17, and a reduction of IFN-γ/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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 17235