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The prognosis of systemic lupus erythematosus (SLE) is unpredictable. This study aimed to examine the regulatory mechanism of the AHR/TET2/NT5E pathway during SLE progression. The AHR, TET2 and NT5E expression levels were examined in T regulatory cells (Tregs) of patients with SLE. The correlation of AHR, TET2 or NT5E expression levels with the immunosuppressive functions of Tregs was analysed. In patients with SLE, the number of CD4+IL2RA−FOXP3+ T cell subset was positively correlated with the SLE disease activity index value and negatively correlated with the AHR and TET2 expression levels in CD4+IL2RA+FOXP3+ Tregs. Transcriptional profiles of 79 patients with SLE obtained from the Gene Expression Omnibus database (GSE61635 dataset) revealed a significant positive correlation between the mRNA expression levels of AHR and TET2. In silico analysis predicted that the TET2 promoter comprises an AHR‐binding site. Kynurenine (KYN) promoted the binding of AHR to the TET2 promoter in Tregs of patients with SLE and Jurkat T cell lines. Furthermore, NT5E expression was significantly downregulated in Tregs of patients with SLE, which can be attributed to the dysregulation of NT5E promoter methylation status induced by downregulated TET2 activity. Furthermore, the Treg immunosuppressive activity, which is mediated through the TET2 and A2AR‐adenosine pathways, in the KYN‐treated group was approximately two‐fold higher than that in the control group. The AHR/TET2/NT5E axis mediates the Treg immunosuppressive activity. These findings provide novel insights for the development of therapeutic approaches for SLE and related autoimmune diseases. [ABSTRACT FROM AUTHOR]

Purpose: DNA methylation is an important epigenetic modification that is frequently altered in cancer. Recent reports showed that the level of 5-hydroxymethylcytosine (5-hmC) was altered in various types of cancers. The influence of DNA methylation in epithelial ovarian cancer (EOC) is not fully understood. Therefore, the aim of the present study was to investigate factors involved in DNA demethylation in EOC compared with normal ovarian tissues. Methods: We examined the expression of 5-hmC, 5-mC, and TET2 by immunohistochemistry in 130 cases of EOC and 40 cases of normal ovarian tissues. We assessed the prognostic values of 5-hmC, 5-mC, and TET2 in clinical outcome of EOC. Results: We discovered a significant decrease in 5-hmC and TET2 expression in EOC compared with normal ovarian tissues. In contrast, there was a significant increase in 5-mC expression in EOC compared with normal ovarian tissues. The expression of 5-hmC, 5-mC, and TET2 correlated with pathologic stage, tumor grading, lymph node metastasis, and vascular thrombosis. Furthermore, decreased level of 5-hmC predicts poor prognosis of EOC patients. The expression of 5-hmC was an independent prognostic factor for overall survival of EOC patients. Conclusions: The data suggest that loss of 5-hmC is an epigenetic event of EOC, and the expression of 5-hmC could serve as a prognostic factor for EOC. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant DNA methylation can lead to genome destabilization and to deregulated gene expression. Recently, 5-hydroxymethylcytosine (5hmC), derived from oxidation of 5-methylcytosine (5mC) by the Ten-Eleven Translocation (TET) enzymes, has been detected. 5hmC is now considered as a new epigenetic DNA modification with relevant roles in cell homeostasis regulating DNA demethylation and transcription. Our aim was to investigate possible changes in the DNA methylation/demethylation machinery in MS. We assessed the expression of enzymes involved in DNA methylation/demethylation in peripheral blood mononuclear cells (PBMCs) from 40 subjects with MS and 40 matched healthy controls. We performed also, DNA methylation analysis of specific promoters and analysis of global levels of 5mC and 5hmC. We show that TET2 and DNMT1 expression is significantly down-regulated in MS PBMCs and it is associated with aberrant methylation of their promoters. Furthermore, 5hmC is decreased in MS PBMCs, probably as a result of the diminished TET2 level. [Copyright &y& Elsevier]