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

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

PROVIDER: PRJNA418112 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6282730.fastq.gz	Fastqsanger.gz
	SRR6282731.fastq.gz	Fastqsanger.gz
	SRR6282722.fastq.gz	Fastqsanger.gz
	SRR6282732.fastq.gz	Fastqsanger.gz
	SRR6282723.fastq.gz	Fastqsanger.gz

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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

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

2018-06-04 | GSE106807 | GEO

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

Project description:Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children (juveniles). Previous studies demonstrated that CD4+ T cells in the mouse lung, whose primary responsibility is coordinating the immune response foreign pathogens, are differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential methylation on CD4+ T cell gene expression and response to infection remains unclear. 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. 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 found 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.

2022-12-22 | GSE214488 | GEO

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

2022-12-22 | GSE214489 | GEO

RNA sequencing of human primary neonatal Naive CD4+ T cells and adult Naive CD4+ T cells treated with Scr or LINE1 ASOs

Project description:RNA sequencing of human neonatal Naive CD4+ T cells and adult Naive CD4+ T cells treated with Scr or LINE1 ASO to assess functional relevance of LINE1 absence in newborns.

2024-08-30 | E-MTAB-13718 | biostudies-arrayexpress

H3K4me3 patterning in neonatal and adult naïve CD4 T cells

Project description:Adult naïve CD4 T cells demonstrate differences in H3K4me3 patterning with H3K4me3 enrichment in T cell activation pathways compared to neonatal cells.

2022-05-17 | GSE202904 | GEO

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