Epigenetics and the adaptive immune response

Kondilis-Mangum, Hrisavgi D.; Wade, Paul A.

doi:10.1016/j.mam.2012.06.008

Cited by 52 publications

(38 citation statements)

References 104 publications

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“…Self-healing of primary infections of P. chabaudi bloodstage malaria generates long-lasting immunity, which manifests itself as much lower parasitemias upon homologous rechallenge in comparison to the corresponding primary infections Wunderlich et al 2014). There is ample evidence that also genes involved in both innate and adaptive immunity are under complex epigenetic control including modifications of DNA methylation (Lim et al 2010;Rodriguez-Cortez et al 2011;Kondilis-Mangum and Wade 2013;Obata et al 2015;Hennessy and McKernan 2016). Insofar, it is rather surprising that protective vaccination and P. chabaudi infections induce changes in the DNA methylation of promoters of so many genes, most of them are related to regulation of transcription, but only very few genes can be related to any functions of the immune system inherent to the liver by gene set enrichment analyses.…”

Section: Discussionmentioning

confidence: 99%

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

et al. 2017

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Epigenetic mechanisms such as DNA methylation are increasingly recognized to be critical for vaccination efficacy and outcome of different infectious diseases, but corresponding information is scarcely available for host defense against malaria. In the experimental blood-stage malaria Plasmodium chabaudi, we investigate the possible effects of a blood-stage vaccine on DNA methylation of gene promoters in the liver, known as effector against blood-stage malaria, using DNA methylation microarrays. Naturally susceptible Balb/c mice acquire, by protective vaccination, the potency to survive P. chabaudi malaria and, concomitantly, modifications of constitutive DNA methylation of promoters of numerous genes in the liver; specifically, promoters of 256 genes are hyper(=up)- and 345 genes are hypo(=down)-methylated (p < 0.05). Protective vaccination also leads to changes in promoter DNA methylation upon challenge with P. chabaudi at peak parasitemia on day 8 post infection (p.i.), when 571 and 1013 gene promoters are up- and down-methylated, respectively, in relation to constitutive DNA methylation (p < 0.05). Gene set enrichment analyses reveal that both vaccination and P. chabaudi infections mainly modify promoters of those genes which are most statistically enriched with functions relating to regulation of transcription. Genes with down-methylated promoters encompass those encoding CX3CL1, GP130, and GATA2, known to be involved in monocyte recruitment, IL-6 trans-signaling, and onset of erythropoiesis, respectively. Our data suggest that vaccination may epigenetically improve parts of several effector functions of the liver against blood-stage malaria, as, e.g., recruitment of monocyte/macrophage to the liver accelerated liver regeneration and extramedullary hepatic erythropoiesis, thus leading to self-healing of otherwise lethal P. chabaudi blood-stage malaria.

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Section: Discussionmentioning

confidence: 99%

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

et al. 2017

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“…It is well established that histone modifications help govern chromatin accessibility to the transcriptional machinery, thereby regulating gene expression (17). In particular, trimethylation of lysine 27 on histone 3 (H3K27me3), which is primarily mediated by the polycomb repressive complex 2 (PRC2), is associated with transcriptional repression in various cells including DCs and macrophages (28, 29).…”

Section: Resultsmentioning

confidence: 99%

“…While the transcriptomes of DC subsets are clearly dependent upon lineage-specific transcription factors (15), epigenetic mechanisms are also essential for regulating gene expression during DC development (16). Epigenetic mechanisms, which include DNA methylation and posttranslational modifications of histone tails, regulate gene expression by governing chromatin accessibility to the transcriptional machinery (17). Although epigenetic modifications of multiple genes have been well-studied in the context of T helper cell differentiation (18–20), remarkably little is known of epigenetic mechanisms that might be expected to influence DC development or function (16).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Control of Ccr7 Expression in Distinct Lineages of Lung Dendritic Cells

Moran

Nakano

Kondilis-Mangum

et al. 2014

The Journal of Immunology

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Adaptive immune responses to inhaled allergens are induced following CCR7-dependent migration of pre-DC (precursor of DC)-derived conventional dendritic cells (cDCs) from the lung to regional lymph nodes (LN). However, monocyte-derived (mo) DCs in the lung express very low levels of Ccr7, and consequently do not migrate efficiently to LN. To investigate the molecular mechanisms that underlie this dichotomy, we studied epigenetic modifications at the Ccr7 locus of murine cDCs and moDCs. When expanded from bone marrow precursors, moDCs were enriched at the Ccr7 locus for trimethylation of histone 3 lysine 27 (H3K27me3), a modification associated with transcriptional repression. Similarly, moDCs prepared from the lung also displayed increased levels of H3K27me3 at the Ccr7 promoter compared with migratory cDCs from that organ. Analysis of DC progenitors revealed that epigenetic modification of Ccr7 does not occur early during DC lineage commitment because monocytes and pre-DCs both had low levels of Ccr7-associated H3K27me3. Rather, Ccr7 is gradually silenced during the differentiation of monocytes to moDCs. Thus, epigenetic modifications of the Ccr7 locus control the migration, and therefore the function of DCs in vivo. These findings suggest that manipulating epigenetic mechanisms might be a novel approach to control DC migration and thereby improve DC-based vaccines and treat inflammatory diseases of the lung.

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“…Th2 cytokine gene loci receive allowable histone marks but the IFN-γ gene locus receives DNA methylation and repressive histone marks including trimethylation of histone H3 lysine 27 (H3K27me3) (Fig. 1) [33]. HS V is found to be DNA methylated in naïve T cells and de novo methylated during Th1 differentiation [34].…”

Section: Microrna Transcriptsmentioning

confidence: 99%

Epigenetic Alterations in Cellular Immunity: New Insights into Autoimmune Diseases

Wang

2017

Cell Physiol Biochem

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Epigenetic modification is an additional regulator in immune responses as the genome-wide profiling somehow fails to explain the sophisticated mechanisms in autoimmune diseases. The effect of epigenetic modifications on adaptive immunity derives from their regulations to induce a permissive or negative gene expression. Epigenetic events, such as DNA methylation, histone modifications and microRNAs (miRNAs) are often found in T cell activation, differentiation and commitment which are the major parts in cellular immunity. Recognizing the complexity of interactions between epigenetic mechanisms and immune disturbance in autoimmune diseases is essential for the exploration of efficient therapeutic targets. In this review, we summarize a list of studies that indicate the significance of dysregulated epigenetic modifications in autoimmune diseases while focusing on T cell immunity.

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Epigenetics and the adaptive immune response

Cited by 52 publications

References 104 publications

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

Epigenetic Control of Ccr7 Expression in Distinct Lineages of Lung Dendritic Cells

Epigenetic Alterations in Cellular Immunity: New Insights into Autoimmune Diseases

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