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.
Highlights
Behcet’s disease (BD) is a systemic autoimmunemediated inflammatory disease
A reduced mRNA expression of interferon regulatory factor 8 (IRF8) and a hypermethylation status of IRF8 promoter was observed in dendritic cells (DCs) from active ocular BD patients as compared to normal controls or inactive BD patients
Our findings revealed that the mRNA expression of IRF8 was notably lower in active ocular BD subjects (*p
Summary
Behcet’s disease (BD) is a systemic autoimmunemediated inflammatory disease. The intraocular inflammation (uveitis) which often occurs in these patients is a serious sight-threatening clinical entity that is often accompanied by recurrent episodes of oral ulceration, genital ulceration and skin lesions [1]. Numerous studies have demonstrated that the pathogenesis of BD is closely related to an enhanced T helper (Th) type 1 and Th17 cell immune response [3,4,5]. The co-stimulatory molecules of DCs facilitate the activation of naïve T cells and initiate a primary immune response. The differentiation of different effector T cells from naïve T cells relies critically upon the particular cytokine environment created by DCs during autoimmune pathology [7, 8]. Various autoimmune inflammatory diseases, such as uveitis, are perceived as being caused by an aberrant immune response in which DCs promote the activation of different subsets of Th cells [6]. Previous studies including work from our team demonstrated that excessive Th1/Th17 responses in ocular BD patients could be inhibited by regulating DC function via immunomodulatory treatments [9,10,11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
