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

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 unkno...

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Autores principales:	Yiguo Qiu, Hongsong Yu, Yunyun Zhu, Zi Ye, Jing Deng, Wencheng Su, Qingfeng Cao, Gangxiang Yuan, Aize Kijlstra, Peizeng Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a6ce99aa5d242e698d7347eee9b4088
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spelling	oai:doaj.org-article:4a6ce99aa5d242e698d7347eee9b40882021-12-02T15:05:58ZHypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease10.1038/s41598-017-01249-72045-2322https://doaj.org/article/4a6ce99aa5d242e698d7347eee9b40882017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01249-7https://doaj.org/toc/2045-2322Abstract 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-1β, 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.Yiguo QiuHongsong YuYunyun ZhuZi YeJing DengWencheng SuQingfeng CaoGangxiang YuanAize KijlstraPeizeng YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yiguo Qiu Hongsong Yu Yunyun Zhu Zi Ye Jing Deng Wencheng Su Qingfeng Cao Gangxiang Yuan Aize Kijlstra Peizeng Yang Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease
description	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-1β, 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.
format	article
author	Yiguo Qiu Hongsong Yu Yunyun Zhu Zi Ye Jing Deng Wencheng Su Qingfeng Cao Gangxiang Yuan Aize Kijlstra Peizeng Yang
author_facet	Yiguo Qiu Hongsong Yu Yunyun Zhu Zi Ye Jing Deng Wencheng Su Qingfeng Cao Gangxiang Yuan Aize Kijlstra Peizeng Yang
author_sort	Yiguo Qiu
title	Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease
title_short	Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease
title_full	Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease
title_fullStr	Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease
title_full_unstemmed	Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease
title_sort	hypermethylation of interferon regulatory factor 8 (irf8) confers risk to vogt-koyanagi-harada disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4a6ce99aa5d242e698d7347eee9b4088
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Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt-Koyanagi-Harada Disease

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