DNA methylation: a promising landscape for immune system-related diseases

Suárez-Álvarez, Beatriz; Rodríguez, Ramón María Alvargonzález; Fraga, Mario F.; López‐Larrea, Carlos

doi:10.1016/j.tig.2012.06.005

Cited by 115 publications

(106 citation statements)

References 99 publications

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“…Widespread dynamic DNA methylation including methylation of genes involved in defense mechanims in response to biotic stress has been observed in Arabidopsis thaliana (Dowen et al 2012). Methylation of genes in stress-modulating limbic-hypothalamic-pituitary-adrenal circuitry such as the neuropeptide corticotrophin-releasing factor (Elliot et al 2010), oxytocin and brain-derived neurotrophic factors (Unternaehrer et al 2012), and the immune system (Suarez-Alvarez et al 2012) has been observed. In animals, methylation of FOXO3 reduces oxidative stress-induced and neuronal apoptosis .…”

Section: Discussionmentioning

confidence: 99%

Lipotropes promote immunobiochemical plasticity and protect fish against low-dose pesticide-induced oxidative stress

Muthappa

Gupta

Yengkokpam

et al. 2014

Cell Stress and Chaperones

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An experiment was conducted to evaluate the role of different lipotropes in modulating immunity and biochemical plasticity under conditions of sublethal low-dose pesticide-induced stress in fish. Labeo rohita fish fingerlings were divided in two sets with one set of fish continuously exposed to low-dose endosulfan (1/10th of 96-h LC 50 ) for 21 days, the other was unexposed, and both sets of fish were fed with practical diets supplemented with either 2 % lecithin, 0.5 % betaine, or 0.1 % choline and compared against unsupplemented diet. Low-dose endosulfan exposure had adverse effects (P<0.05/P<0.01) on hematological profile (erythrocyte count, hemoglobin, and hematocrit), serum protein (total protein, albumin, and globulin) and lipid profile (cholesterol and triglyceride), anti-oxidative status (ascorbic acid content of muscle, liver, brain, and kidney and activity of anti-oxidative enzymes: catalase and superoxide dismutase), neurotransmission (acetylcholinesterase activity in muscle and brain), immunological attributes (WBC count, albumin to globulin ratio, phagocytic activity, and serum cortisol), and metabolic plasticity as revealed from enzyme activities (muscle lactate dehydrogenase, liver and kidney glucose-6-phosphatase dehydrogenase-G6PDH activity). Dietary lipotropes prevented these effects completely or partially and the effects were lipotrope dependent. Kinetics (maximum velocity value V max , catalytic efficiency and Michaelis constant K m ) of G6PDH enzyme from crude extracts of liver and kidney indicated inhibition due to endosulfan but lipotropes could protect enzyme and showed a stabilizing effect. The supplements also helped maintain integrity of histoarchitecture of the hepatocytes in endosulfan-exposed fish to a great extent. Feeding lipotropes to fish reared in endosulfan-free water also improved hematological and serum protein and lipid profiles and were immunostimulatory. In conclusion, dietary lipotropes, especially betaine and lecithin at the levels used, improve erythropoiesis, serum protein and lipid profile, anti-oxidant status, immunocompetence, neurotransmission, and protect the livers of L. rohita fingerlings even when continuously exposed to low-dose endosulfan.

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Section: Discussionmentioning

confidence: 99%

Lipotropes promote immunobiochemical plasticity and protect fish against low-dose pesticide-induced oxidative stress

Muthappa

Gupta

Yengkokpam

et al. 2014

Cell Stress and Chaperones

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“…After an IBDV infection macrophages and T-cells are known to infiltrate the BF [23,36] and it is conceivable that these immune cell types are contributing to the observed increase in bursal 5hmC levels and Tet 1 and 2 mRNAs. In support of this view is the finding that both activation of macrophages and T-cells causes genomic demethylation events which may include the involvement of elevated 5hmC levels and altered Tet function [37]. Furthermore, there is an emerging concept that pro-inflammatory cytokines may modulate Tet expression and 5hmC levels to cause transcriptional changes in cytokine responsive genes [27].…”

Section: Discussionmentioning

confidence: 98%

A B-cell targeting virus disrupts potentially protective genomic methylation patterns in lymphoid tissue by increasing global 5-hydroxmethylcytosine levels

Ciccone¹,

Mwangi²,

Ruzov³

et al. 2014

Vet Res

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The mechanisms by which viruses modulate the immune system include changes in host genomic methylation. 5-hydroxymethylcytosine (5hmC) is the catalytic product of the Tet (Ten-11 translocation) family of enzymes and may serve as an intermediate of DNA demethylation. Recent reports suggest that 5hmC may confer consequences on cellular events including the pathogenesis of disease; in order to explore this possibility further we investigated both 5-methylcytosine (5mC) and 5hmC levels in healthy and diseased chicken bursas of Fabricius. We discovered that embryonic B-cells have high 5mC content while 5hmC decreases during bursa development. We propose that a high 5mC level protects from the mutagenic activity of the B-cell antibody diversifying enzyme activation induced deaminase (AID). In support of this view, AID mRNA increases significantly within the developing bursa from embryonic to post hatch stages while mRNAs that encode Tet family members 1 and 2 reduce over the same period. Moreover, our data revealed that infectious bursal disease virus (IBDV) disrupts this genomic methylation pattern causing a global increase in 5hmC levels in a mechanism that may involve increased Tet 1 and 2 mRNAs. To our knowledge this is the first time that a viral infection has been observed to cause global increases in genomic 5hmC within infected host tissues, underlining a mechanism that may involve the induction of B-cell genomic instability and cell death to facilitate viral egress.

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“…Accumulating evidence suggests that DNA methylation play critical roles in the maintenance of both self-renewing hematopoietic stem cells and leukemic stem cells [29]. Changes in the DNA methylation profile have a critical role in the division of these stem cells into the myeloid and lymphoid lineages and in the establishment of a specific phenotype and functionality in each terminally differentiated cell type [30]. HSCs deficient in both Dnmt3a and 3b show a loss of proliferative ability but retain differentiation potential, suggesting de novo methylation is important for self-renewal in HSCs [28].…”

Section: Hematopoietic Stem Cellsmentioning

confidence: 99%

“…HSCs deficient in both Dnmt3a and 3b show a loss of proliferative ability but retain differentiation potential, suggesting de novo methylation is important for self-renewal in HSCs [28]. The aberrant DNA methylation has been associated with several immune deficiencies and autoimmune disorders [30].…”

Section: Hematopoietic Stem Cellsmentioning

confidence: 99%