Ocular Behcet’s disease is associated with aberrant methylation of interferon regulatory factor 8 (IRF8) in monocyte-derived dendritic cells
Metrics: HTML 1073 views | ?
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
Peizeng Yang, email: firstname.lastname@example.org
Keywords: DNA methylation, interferon regulatory factor 8, Behcet’s disease, dendritic cells
Received: February 15, 2017 Accepted: March 28, 2017 Published: April 19, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.