Oxidative stress and dietary micronutrient deficiencies contribute to overexpression of epigenetically regulated genes by lupus T cells

Ray, Donna; Strickland, Faith M.; Richardson, Bruce C.

doi:10.1016/j.clim.2018.04.003

Cited by 19 publications

(15 citation statements)

References 32 publications

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“…A mechanistic rationale exists for evaluating these 4 dietary scores in relation to SLE onset. Oxidative stress and other environmental exposures, including diet, can contribute to lupus onset and flares through epigenetic mechanisms that modify CD4+ T cell gene expression (33). Although we did not demonstrate that high adherence to the AHEI‐2010 or aMed dietary scores reduces the risk of SLE, our results demonstrate a potential reduction in SLE risk with high nut/legume intake, which also includes soy products.…”

Section: Discussionmentioning

confidence: 99%

Association of Dietary Quality With Risk of Incident Systemic Lupus Erythematosus in the Nurses’ Health Study and Nurses’ Health Study II

Barbhaiya

Tedeschi

Leatherwood

et al. 2021

Arthritis Care & Research

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Objective Knowledge remains scarce regarding diet and systemic lupus erythematosus (SLE) risk. Our objective was to investigate 4 dietary quality scores and SLE risk overall and by anti–double‐stranded DNA (anti‐dsDNA) positive versus negative subtypes. Methods We studied 79,568 women in the Nurses’ Health Study (1984–2014) and 93,554 in the Nurses’ Health Study II (1991–2013). Using validated food frequency questionnaires, we calculated 4 dietary scores: the 2010 Alternative Healthy Eating Index (AHEI‐2010), the Alternative Mediterranean Diet Score (aMed), the Dietary Approach to Stop Hypertension (DASH), and the Empirical Dietary Inflammatory Pattern (EDIP). Incident SLE was confirmed by medical record review. Time‐varying Cox regression models estimated pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SLE risk, overall and by anti‐dsDNA, for cumulative average dietary quality score tertiles and individual AHEI‐2010 components. Results We identified 194 incident SLE cases. SLE risk was similar in women with the highest (versus lowest) dietary scores (AHEI‐2010 HR 0.78 [95% CI 0.54–1.14], aMed HR 0.82 [95% CI 0.56–1.18], DASH HR 1.16 [95% CI 0.81–1.66], EDIP HR 0.83 [95% CI 0.57–1.21]). No association was demonstrated for anti‐dsDNA+ or anti‐dsDNA– SLE risk. Women in the highest (versus lowest) AHEI‐2010 tertile of nut/legume intake had a decreased SLE risk (HR 0.59 [95% CI 0.40–0.87]). No association was demonstrated for other AHEI‐2010 components and SLE risk. Conclusion We observed no association between long‐term adherence to the AHEI‐2010, aMed, DASH, or EDIP scores with SLE risk, suggesting a large effect of dietary quality on SLE risk is unlikely. However, potential reduction in overall SLE risk with high nut/legume intake warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Association of Dietary Quality With Risk of Incident Systemic Lupus Erythematosus in the Nurses’ Health Study and Nurses’ Health Study II

Barbhaiya

Tedeschi

Leatherwood

et al. 2021

Arthritis Care & Research

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“…A great deal of evidence has shown that aberrant epigenetic modifications contribute to CD4 + T cell activation and the pathogenesis of SLE [4,[41][42][43]. The epigenetic regulator UHRF1 typically alters DNA methylation and histone modification to regulate gene expression.…”

Section: Discussionmentioning

confidence: 99%

UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE

Liu

Yang

et al. 2021

Clin Epigenet

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Background Transcription factor B cell lymphoma 6 (BCL6) is a master regulator of T follicular helper (Tfh) cells, which play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanisms by which BCL6 expression is regulated are poorly understood. Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important epigenetic factor that regulates DNA methylation and histone modifications. In the present study, we assessed whether UHRF1 can regulate BCL6 expression and influence the differentiation and proliferation of Tfh cells. Results Compared to healthy controls, the mean fluorescence intensity of UHRF1 (UHRF1-MFI) in Tfh cells from SLE patients was significantly downregulated, whereas that of BCL6 (BCL6-MFI) was significantly upregulated. In vitro, UHRF1 knockdown led to BCL6 overexpression and promoted Tfh cell differentiation. In contrast, UHRF1 overexpression led to BCL6 downregulation and decreased Tfh cell differentiation. In vivo, conditional UHRF1 gene knockout (UHRF1-cKO) in mouse T cells revealed that UHRF1 depletion can enhance the proportion of Tfh cells and induce an augmented GC reaction in mice treated with NP-keyhole limpet hemocyanin (NP-KLH). Mechanistically, UHRF1 downregulation can decrease DNA methylation and H3K27 trimethylation (H3K27me3) levels in the BCL6 promoter region of Tfh cells. Conclusions Our results demonstrated that UHRF1 downregulation leads to increased BCL6 expression by decreasing DNA methylation and H3K27me3 levels, promoting Tfh cell differentiation in vitro and in vivo. This finding reveals the role of UHRF1 in regulating Tfh cell differentiation and provides a potential target for SLE therapy.

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“…Nevertheless, diet supplemented with vitamins (A, B6, C, D or E) resulted in improvement of flares and symptoms of SLE (10) . Ray et al (2018) hypothesised that expression of genes susceptible to DNA methylation in T cells from SLE patients may be more prevalent in low-micronutrient conditions than in healthy T cells. They cultured CD4 þ T cells from lupus patients PHA-stimulated in culture media with normal or low levels of B6 and B12 vitamins, methionine, folate and choline, and then measured expression of CD70, perforin and KIR (171) .…”

Section: Diet Epigenetic and Sle Linkagementioning

confidence: 99%

“…Ray et al (2018) hypothesised that expression of genes susceptible to DNA methylation in T cells from SLE patients may be more prevalent in low-micronutrient conditions than in healthy T cells. They cultured CD4 þ T cells from lupus patients PHA-stimulated in culture media with normal or low levels of B6 and B12 vitamins, methionine, folate and choline, and then measured expression of CD70, perforin and KIR (171) . It should be noted that KIR, perforin and CD70 genes are usually hypermethylated and overexpressed in SLE (58,(125)(126)(127)(128) .…”

Section: Diet Epigenetic and Sle Linkagementioning

confidence: 99%

Epigenetic linkage of systemic lupus erythematosus and nutrition

et al. 2021

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The term “epigenetics” refers to a series of meiotically/mitotically inheritable alterations in gene expression, related to environmental factors, without disruption on DNA sequences of bases. Recently, the pathophysiology of autoimmune diseases (ADs) has been closely linked to epigenetic modifications. Actually, epigenetic mechanisms can modulate gene expression or repression of targeted cells and tissues involved in autoimmune/inflammatory conditions acting as keys effectors in regulation of adaptive and innate responses. ADs, as systemic lupus erythematosus (SLE), a rare disease that still lacks effective treatment, is characterized by epigenetic marks in affected cells. Taking into account that epigenetic mechanisms have been proposed as a winning strategy in the search of new more specific and personalized therapeutics agents. Thus, pharmacology and pharmacoepigenetic studies about epigenetic regulations of ADs may provide novel individualized therapies. Focussing in possible implicated factors on development and predisposition of SLE, diet is feasibly one of the most important factors since it is linked directly to epigenetic alterations and these epigenetic changes may augment or diminish the risk of SLE. Nevertheless, several studies have guaranteed that dietary therapy could be a promise to SLE patients via prophylactic actions deprived of side effects of pharmacology, decreasing co-morbidities and improving lifestyle of SLE sufferers. Herein, we review and discuss the cross-link between epigenetic mechanisms on SLE predisposition and development, as well as the influence of dietary factors on regulation epigenetic modifications that would eventually make a positive impact on SLE patients.

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Oxidative stress and dietary micronutrient deficiencies contribute to overexpression of epigenetically regulated genes by lupus T cells

Cited by 19 publications

References 32 publications

Association of Dietary Quality With Risk of Incident Systemic Lupus Erythematosus in the Nurses’ Health Study and Nurses’ Health Study II

Association of Dietary Quality With Risk of Incident Systemic Lupus Erythematosus in the Nurses’ Health Study and Nurses’ Health Study II

UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE

Epigenetic linkage of systemic lupus erythematosus and nutrition

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