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Series GSE60114 Query DataSets for GSE60114
Status Public on Mar 16, 2015
Title Linking the aryl hydrocarbon receptor with altered DNA methylation patterns and developmentally induced aberrant antiviral T cell responses [RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Successfully fighting infection requires a properly tuned immune system. Recent epidemiological studies link exposure to pollutants that bind the aryl hydrocarbon receptor (AHR) during development with poorer immune responses later in life. Yet, how developmental triggering of AHR durably alters immune cell function remains unknown. Using a mouse model, we show that developmental activation of AHR leads to long-lasting reduction in the response of CD8+ T cells during influenza virus infection, cells critical for resolving primary infection. Combining genome-wide approaches, we demonstrate that developmental activation alters DNA methylation and gene expression patterns in isolated CD8+ T cells prior to and during infection. Altered transcriptional profiles in CD8+ T cells from developmentally exposed mice reflect changes in pathways involved in proliferation and immunoregulation, with an overall pattern that bears hallmarks of T cell exhaustion. Developmental exposure also changed DNA methylation across the genome, but differences were most pronounced following infection, where we observed inverse correlation between promoter methylation and gene expression. This points to altered regulation of DNA methylation as one mechanism by which AHR causes durable changes in T cell function. Discovering that distinct gene sets and pathways were differentially changed in developmentally exposed mice prior to and after infection further reveals that the process of CD8+ T cell activation is rendered fundamentally different by early life AHR signaling. These findings reveal a novel role for AHR in the developing immune system: regulating DNA methylation and gene expression as immune cells respond to viral infection later in life.
Overall design In this study, two biological replicates were collected for each of four treatment groups: developmental exposure to vehicle control (Veh) and naïve, developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and naïve, developmental exposure to Veh and infected, developmental exposure to TCDD and infected. For each sample, both RNA-seq and methylated DNA immunoprecipitation (MeDIP)-seq were performed.
Contributor(s) Winans B, Nagari A, Chae M, Ko C, Puga A, Kraus WL, Lawrence BP
Citation(s) 25810390
Submission date Aug 05, 2014
Last update date May 15, 2019
Contact name B Paige Lawrence
Organization name University of Rochester Medical Center
Department Environmental Medicine
Street address 575 Elmwood Ave.
City Rochester
State/province NY
ZIP/Postal code 14642
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (8)
GSM1465125 Sample_3
GSM1465126 Sample_5
GSM1465127 Sample_6
This SubSeries is part of SuperSeries:
GSE60115 Linking the aryl hydrocarbon receptor with altered DNA methylation patterns and developmentally induced aberrant antiviral T cell responses
BioProject PRJNA257507
SRA SRP045275

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Supplementary file Size Download File type/resource
GSE60114_Flu_TCDD.bedGraph.gz 126.9 Mb (ftp)(http) BEDGRAPH
GSE60114_Flu_VEH.bedGraph.gz 125.7 Mb (ftp)(http) BEDGRAPH
GSE60114_Naive_TCDD.bedGraph.gz 110.0 Mb (ftp)(http) BEDGRAPH
GSE60114_Naive_VEH.bedGraph.gz 111.6 Mb (ftp)(http) BEDGRAPH
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