Metabolic regulation of epigenetic remodeling in immune cells

Britt, Emily C; John, Steven V.; Locasale, Jason W.; Fan, Jianqing

doi:10.1016/j.copbio.2019.12.008

Cited by 26 publications

(17 citation statements)

References 57 publications

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“…5). Emerging data have shown the beneficial effects of HDAC inhibitors in inflammation-related diseases [39][40][41][42][43] and recent research supports the interplay between lipid metabolism and lysine acetylation during inflammation responses 20,44,45 with acetyl coenzyme A (acetyl-CoA), a key intermediary metabolite in lipid metabolism, being the main substrate for lysine acetylation by histone acetyltransferases (HATs) 45,46 . On the contrary, HDAC-containing protein complexes catalyze the removal of N-acetyl groups from lysine residues 47 which activity and expression is increased during microglial activation and particularly important for TLR-activated inflammatory responses 23,48 .…”

Section: Maldi-tof Ms-based Cell Fingerprinting Detects Changes In Lp...mentioning

confidence: 99%

LPS-induced lipid alterations in microglia revealed by MALDI mass spectrometry-based cell fingerprinting in neuroinflammation studies

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2022

Sci Rep

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Pathological microglia activation can promote neuroinflammation in many neurodegenerative diseases, and it has therefore emerged as a potential therapeutic target. Increasing evidence suggests alterations in lipid metabolism as modulators and indicators in microglia activation and its effector functions. Yet, how lipid dynamics in activated microglia is affected by inflammatory stimuli demands additional investigation to allow development of more effective therapies. Here, we report an extensive matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) whole cell fingerprinting workflow to investigate inflammation-associated lipid patterns in SIM-A9 microglial cells. By combining a platform of three synergistic MALDI MS technologies we could detect substantial differences in lipid profiles of lipopolysaccharide (LPS)- stimulated and unstimulated microglia-like cells leading to the identification of 21 potential inflammation-associated lipid markers. LPS-induced lipids in SIM-A9 microglial cells include phosphatidylcholines, lysophosphatidylcholines (LysoPC), sphingolipids, diacylglycerols and triacylglycerols. Moreover, MALDI MS-based cell lipid fingerprinting of LPS-stimulated SIM-A9 microglial cells pre-treated with the non-selective histone deacetylase inhibitor suberoylanilide hydroxamic acid revealed specific modulation of LPS-induced-glycerolipids and LysoPC(18:0) with a significant reduction of microglial inflammation response. Our study introduces MALDI MS as a complementary technology for fast and label-free investigation of stimulus-dependent changes in lipid patterns and their modulation by pharmaceutical agents.

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Section: Maldi-tof Ms-based Cell Fingerprinting Detects Changes In Lp...mentioning

confidence: 99%

LPS-induced lipid alterations in microglia revealed by MALDI mass spectrometry-based cell fingerprinting in neuroinflammation studies

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Enzlein

Hopf

2022

Sci Rep

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“…Kinetic evidence shows that epigenetic remodelling plays a central role in mediating the transcriptional programme for activation of immune cells and immune memory, allowing the diet to influence immune function (135) . It is also worth remembering that genetic encoding is related to the individual response to diets, and this specificity must differentiate recommendations and nutritional guidelines.…”

Section: The Relation Between Dietary Patterns Epigenetic Modificatimentioning

confidence: 99%

Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2

et al. 2020

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COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recognized by the World Health Organization (WHO) as a pandemic in 2020. Host preparation to combat the virus is an important strategy to avoid COVID-19 severity. Thus, the relationship between eating habits, nutritional status, and their effects on the immune response and further implications in viral respiratory infections are important topics discussed in this revision. Malnutrition causes the most diverse alterations in the immune system, suppressing of the immune response and increasing the susceptibility to infections as SARS-CoV-2. On the other hand, obesity induces low-grade chronic inflammation caused by excess adiposity, which increases angiotensin-converting enzyme 2 (ACE2). It decreases the immune response favoring SARS-CoV-2 virulence and promoting respiratory distress syndrome. The present review highlights the importance of food choices considering their inflammatory effects, consequently increasing the viral susceptibility observed in malnutrition and obesity. Healthy eating habits, micronutrients, bioactive compounds, and probiotics are strategies for COVID-19 prevention. Therefore, a diversified and balanced diet can contribute to the improvement of the immune response to viral infections such as COVID-19.

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“…A recent study also indicated that the loss of 2-HG production directly reduced methylation of the Foxp3 gene locus, increasing Fox3 expression, thus reprograms T H 17 differentiation towards Treg cells (133). Moreover, low glucose availability in TME restricts acetyl-CoA level, the acetyl group donor for histone acetylation (134), and Qiu et al demonstrated that acetate supplementation rescued CD8+ T cell effector function in a glucose restricted environment by promoting histone acetylation and chromatin accessibility thus promoting IFN-g production of T cells in TME (135). Besides glucose restriction, glutamine deprivation resulted in the differentiation of immunosuppressive regulatory T (Treg) cells from naive CD4+ T cells due to the loss of a-ketoglutarate (aKG), the glutaminederived metabolite that is needed for DNA demethylation and regulates CD4+ T cell T H 1 differentiation.…”

Section: Tme Metabolites Epigenetically Reprogram Both Innate and Adaptive Immune Effector Cellsmentioning

confidence: 99%

Metabolites in the Tumor Microenvironment Reprogram Functions of Immune Effector Cells Through Epigenetic Modifications

2021

Front. Immunol.

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Cellular metabolism of both cancer and immune cells in the acidic, hypoxic, and nutrient-depleted tumor microenvironment (TME) has attracted increasing attention in recent years. Accumulating evidence has shown that cancer cells in TME could outcompete immune cells for nutrients and at the same time, producing inhibitory products that suppress immune effector cell functions. Recent progress revealed that metabolites in the TME could dysregulate gene expression patterns in the differentiation, proliferation, and activation of immune effector cells by interfering with the epigenetic programs and signal transduction networks. Nevertheless, encouraging studies indicated that metabolic plasticity and heterogeneity between cancer and immune effector cells could provide us the opportunity to discover and target the metabolic vulnerabilities of cancer cells while potentiating the anti-tumor functions of immune effector cells. In this review, we will discuss the metabolic impacts on the immune effector cells in TME and explore the therapeutic opportunities for metabolically enhanced immunotherapy.

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Metabolic regulation of epigenetic remodeling in immune cells

Cited by 26 publications

References 57 publications

LPS-induced lipid alterations in microglia revealed by MALDI mass spectrometry-based cell fingerprinting in neuroinflammation studies

LPS-induced lipid alterations in microglia revealed by MALDI mass spectrometry-based cell fingerprinting in neuroinflammation studies

Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2

Metabolites in the Tumor Microenvironment Reprogram Functions of Immune Effector Cells Through Epigenetic Modifications

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