Oncotarget

Research Papers:

Histone demethylase JMJD3 regulates CD11a expression through changes in histone H3K27 tri-methylation levels in CD4+ T cells of patients with systemic lupus erythematosus

Heng Yin, Haijing Wu, Ming Zhao, Qing Zhang, Hai Long, Siqi Fu and Qianjin Lu _

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Oncotarget. 2017; 8:48938-48947. https://doi.org/10.18632/oncotarget.16894

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Abstract

Heng Yin1, Haijing Wu1, Ming Zhao1, Qing Zhang1, Hai Long1, Siqi Fu1 and Qianjin Lu1

1Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China

Correspondence to:

Qianjin Lu, email: qianlu5860@gmail.com

Keywords: JMJD3, H3K27me3, CD11a, SLE, CD4+ T cells

Received: February 13, 2017     Accepted: March 28, 2017     Published: April 06, 2017

ABSTRACT

Aberrant CD11a overexpression in CD4+ T cells induces T cell auto-reactivity, which is an important factor for systemic lupus erythematosus (SLE) pathogenesis. Although many studies have focused on CD11a epigenetic regulation, little is known about histone methylation. JMJD3, as a histone demethylase, is capable of specifically removing the trimethyl group from the H3K27 lysine residue, triggering target gene activation. Here, we examined the expression and function of JMJD3 in CD4+ T cells from SLE patients. Significantly decreased H3K27me3 levels and increased JMJD3 binding were detected within the ITGAL (CD11a) promoter locus in SLE CD4+ T cells compared with those in healthy CD4+ T cells. Moreover, overexpressing JMJD3 through the transfection of pcDNA3.1-JMJD3 into healthy donor CD4+ T cells increased JMJD3 enrichment and decreased H3K27me3 enrichment within the ITGAL (CD11a) promoter and up-regulated CD11a expression, leading to T and B cell hyperactivity. Inhibition of JMJD3 via JMJD3-siRNA in SLE CD4+ T cells showed the opposite effects. These results demonstrated that histone demethylase JMJD3 regulates CD11a expression in lupus T cells by affecting the H3K27me3 levels in the ITGAL (CD11a) promoter region, and JMJD3 might thereby serve as a potential therapeutic target for SLE.


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