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DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE106807 | GEO | 2018/06/04

REPOSITORIES: GEO

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DNA methylation regulates the neonatal CD4<sup>+</sup> T-cell response to pneumonia in mice.

Project description:Pediatric acute lung injury, usually because of pneumonia, has a mortality rate of more than 20% and an incidence that rivals that of all childhood cancers combined. CD4+ T-cells coordinate the immune response to pneumonia but fail to function robustly among the very young, who have poor outcomes from lung infection. We hypothesized that DNA methylation represses a mature CD4+ T-cell transcriptional program in neonates with pneumonia. Here, we found that neonatal mice (3-4 days old) aspirated with Escherichia coli bacteria had a higher mortality rate than juvenile mice (11-14 days old). Transcriptional profiling with an unsupervised RNA-Seq approach revealed that neonates displayed an attenuated lung CD4+ T-cell transcriptional response to pneumonia compared with juveniles. Unlike neonates, juveniles up-regulated a robust set of canonical T-cell immune response genes. DNA methylation profiling with modified reduced representation bisulfite sequencing revealed 44,119 differentially methylated CpGs, which preferentially clustered around transcriptional start sites and CpG islands. A methylation difference-filtering algorithm detected genes with a high likelihood of differential promoter methylation regulating their expression; these 731 loci encoded important immune response and tissue-protective T-cell pathway components. Disruption of DNA methylation with the hypomethylating agent decitabine induced plasticity in the lung CD4+ T-cell marker phenotype. Altogether, multidimensional profiling suggested that DNA methylation within the promoters of a core set of CD4+ T-cell pathway genes contributes to the hyporesponsive neonatal immune response to pneumonia. These findings also suggest that DNA methylation could serve as a mechanistic target for disease-modifying therapies in pediatric lung infection and injury.

| S-EPMC6066312 | biostudies-literature

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Project description:Lung CD4+ T cell responses may determine outcomes in pediatric pnuemonia. We therefore sought to define the transcriptional response and underlying DNA methyaltion landscape of lung CD4+ T cells by treating neonatal (~5 days of age) and juvenile (~15 days of age) mice with 2.8 million CFUs of E. coli or PBS (control) by aspiration. 48 hours later, lung CD4+ T cells were isolated by magnetic bead pre-enrichment and fluorescence-activated cell sorting for RNA-sequencing (RNA-seq) and modified reduced representation bisulfite sequencing (mRRBS).

2018-06-04 | GSE106806 | GEO

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

2018-06-04 | GSE106805 | GEO

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Project description:DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

| PRJNA418111 | ENA

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Project description:DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

| PRJNA418112 | ENA

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Project description:DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

| PRJNA418097 | ENA

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+ T cells of neonatal mice with E. coli pneumonia

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-22 | GSE214490 | GEO

Gene expression and DNA methylation profiling in the seminal vesicles (SVs) from neonatal DES-treated mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-03-27 | GSE102450 | GEO

DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4<sup>+</sup> T cells of neonatal mice with E. coli pneumonia.

Project description:Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children. Previous studies demonstrated that the DNA of CD4+ T cells in the mouse lung, whose primary responsibility is to coordinate the immune response to foreign pathogens, is differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential DNA methylation on CD4+ T cell gene expression and response to infection remains unclear. Here we treated E. coli-infected neonatal (4-day-old) and juvenile (13-day-old) mice with decitabine (DAC), a DNA methyltransferase inhibitor with broad-spectrum DNA demethylating activity, and performed simultaneous genome-wide DNA methylation and transcriptional profiling on lung CD4+ T cells. We show that juvenile and neonatal mice experienced differential demethylation in response to DAC treatment, with larger methylation differences observed in neonates. By cross-filtering differentially expressed genes between juveniles and neonates with those sites that were demethylated in neonates, we find that interferon-responsive genes such as Ifit1 are the most down-regulated methylation-sensitive genes in neonatal mice. DAC treatment shifted neonatal lung CD4+ T cells toward a gene expression program similar to that of juveniles. Following lung infection with E. coli, lung CD4+ T cells in neonatal mice exhibit epigenetic repression of important host defense pathways, which are activated by inhibition of DNA methyltransferase activity to resemble a more mature profile.

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Defining CD4 T Cell Memory by the Epigenetic Landscape of CpG DNA Methylation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-01-20 | E-GEOD-59860 | biostudies-arrayexpress