17β-oestradiol enhances global DNA hypomethylation in CD4-positive T cells from female patients with lupus, through overexpression of oestrogen receptor-α-mediated downregulation of DNMT1

Wu, Zhouwei; Sun, Yue; Mei, Xingyu; Zhang, C.; Pan, Weihua; Shi, Weimin

doi:10.1111/ced.12346

Cited by 25 publications

(15 citation statements)

References 19 publications

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“…One potential mechanism is the epigenetic regulation of ERα in the brain by maternal HFD, which has previously been demonstrated with maternal behaviors and endocrine disruptors 86, 87 . Furthermore, ERα signaling regulates DNA methylation through the control of DNMT genes and other epigenetic factors in a variety of tissues 88–90 . The loss of ERα-induced epigenetic modifications along with the modulation of neurogenesis 31–33 and neural stem cell proliferation and differentiation 34 during development may abrogate the effects of maternal HFD.…”

Section: Discussionmentioning

confidence: 99%

Loss of ERα partially reverses the effects of maternal high-fat diet on energy homeostasis in female mice

Roepke

Yasrebi

Villalobos

et al. 2017

Sci Rep

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Maternal high-fat diet (HFD) alters hypothalamic developmental programming and disrupts offspring energy homeostasis in rodents. 17β-estradiol (E2) also influences hypothalamic programming through estrogen receptor (ER) α. Therefore, we hypothesized that females lacking ERα would be more susceptible to maternal HFD. To address this question, heterozygous ERα knockout (WT/KO) dams were fed a control breeder chow diet (25% fat) or a semi-purified HFD (45% fat) 4 weeks prior to mating with WT/KO males or heterozygous males with an ERα DNA-binding domain mutation knocked in (WT/KI) to produce WT, ERα KO, or ERα KIKO females lacking ERE-dependent ERα signaling. Maternal HFD increased body weight in WT and KIKO, in part, due to increased adiposity and daytime carbohydrate utilization in WT and KIKO, while increasing nighttime fat utilization in KO. Maternal HFD also increased plasma leptin, IL-6, and MCP-1 in WT and increased arcuate expression of Kiss1 and Esr1 (ERα) and liver expression of G6pc and Pepck in WT and KIKO. Contrary to our hypothesis, these data suggest that loss of ERα signaling blocks the influence of maternal HFD on energy homeostasis, inflammation, and hypothalamic and liver gene expression and that restoration of ERE-independent ERα signaling partially reestablishes susceptibility to maternal HFD.

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Section: Discussionmentioning

confidence: 99%

Loss of ERα partially reverses the effects of maternal high-fat diet on energy homeostasis in female mice

Roepke

Yasrebi

Villalobos

et al. 2017

Sci Rep

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“…Estrogen downregulates DNA methyl transferase (DNMT) 1 expression and enhances global DNA hypomethylation in CD4 T cells from female SLE patients. While plasma β-estradiol levels were similar between patients and healthy controls, the mRNA expression of ERα but not ERβ was increased in SLE CD4 T cells ( 70 ). Aberrant extracellular regulated kinase (ERK)/MAPK signaling and resultant decrease in DNMT levels leading to DNA hypomethylation of a number of genes has been described and associated with autoimmune disease pathogenesis ( 71 ).…”

Section: Estrogen and T Lymphocytesmentioning

confidence: 99%

Sex Hormones in Acquired Immunity and Autoimmune Disease

2018

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Women have stronger immune responses to infections and vaccination than men. Paradoxically, the stronger immune response comes at a steep price, which is the high incidence of autoimmune diseases in women. The reasons why women have stronger immunity and higher incidence of autoimmunity are not clear. Besides gender, sex hormones contribute to the development and activity of the immune system, accounting for differences in gender-related immune responses. Both innate and adaptive immune systems bear receptors for sex hormones and respond to hormonal cues. This review focuses on the role of sex hormones particularly estrogen, in the adaptive immune response, in health, and autoimmune disease with an emphasis on systemic lupus erythematosus.

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“…Wu et al . found that 17β‐oestradiol down‐regulated DNMT1 activity and enhanced global DNA hypomethylation in female SLE CD4 + T cells . In recent years, several studies have indicated that demethylation of inflammatory cytokine genes, such as interleukin (IL)−10, IL‐13, IL‐4 and IL‐6, in CD4 + T cells might participate in the progression of SLE .…”

Section: Dna Methylation Alterations In Lupusmentioning

confidence: 99%

“…Furthermore, killer-cell immunoglobulin-like receptors (KIRs), a family of cell surface proteins expressed on natural killer (NK) cells, and a small portion of T cells, are suppressed primarily by DNA methylation in CD4 1 T cells, enhancing production of IFN-g and macrophage in lupus patients [29,30]. Wu et al found that 17b-oestradiol down-regulated DNMT1 activity and enhanced global DNA hypomethylation in female SLE CD4 1 T cells [31]. In recent years, several studies have indicated that demethylation of inflammatory cytokine genes, such as interleukin (IL)210, IL-13, IL-4 and IL-6, in CD4 1 T cells might participate in the progression of SLE [32,33].…”

Section: Abnormal Dna Methylation In Lupus T Cellsmentioning

confidence: 99%

DNA methylation alterations in the pathogenesis of lupus

Chen

et al. 2016

Clinical and Experimental Immunology

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Although lupus is, by definition, associated with genetic and immunological factors, its molecular mechanisms remain unclear. The up-to-date research findings point out that various genetic and epigenetic factors, especially gene-specific and site-specific methylation, are believed to contribute to the initiation and development of systemic lupus erythematosus (SLE). This review presents and summarizes the association between abnormal DNA methylation of immune-related cells and lupus-like diseases, as well as the possible mechanisms of immune disorder caused by DNA methylation, aiming at a better understanding of the roles of aberrant DNA methylation in the initiation and development of certain forms of lupus and providing a new insight into promising therapeutic regimens in lupus-like diseases.

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17β-oestradiol enhances global DNA hypomethylation in CD4-positive T cells from female patients with lupus, through overexpression of oestrogen receptor-α-mediated downregulation of DNMT1

Abstract: 17β-oestradiol enhances global DNA hypomethylation in female SLE CD4+ T cells via downregulation of DNMT1 mediated by ERα overexpression.

Cited by 25 publications

References 19 publications

Loss of ERα partially reverses the effects of maternal high-fat diet on energy homeostasis in female mice

Loss of ERα partially reverses the effects of maternal high-fat diet on energy homeostasis in female mice

Sex Hormones in Acquired Immunity and Autoimmune Disease

DNA methylation alterations in the pathogenesis of lupus

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