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Series GSE102045 Query DataSets for GSE102045
Status Public on Jul 19, 2018
Title G-Protein-Coupled Receptor 68 Negatively Regulates IL-22 Production in Human Th17 Cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Purpose: To identify novel genes regulated by the aryl hydrocarbon receptor that influence human Th17 cell function.
Methods: Naïve CD4 T cells from peripheral blood of six healthy human volunteers were cultured under four experimental conditions for three days: anti-CD3 and anti-CD28 antibodies (Media control), Media with Th17 conditions (IL-6, TGF-b, IL-1b, IL-23), Th17+FICZ and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. A total of six donors were analyzed.
Results: AhR activation with FICZ suppressed IL-17 production from human CD4 T cells and increased IL-22. AhR inhibition with CH223191 potently suppressed IL-22 and modestly increased IL-17 production. On day 3, the number of significantly regulated genes for each treatment were 975 (Th17), 88 (Th17+FICZ) and 142 (Th17+CH223191). 11 common genes were significantly regulated by all three treatments. One of these, GPR68, was investigated further in functional studies since its expression correlated with IL-22 production. Activation of GPR68 with a positive allosteric modulator suppressed IL-22 concentrations in human Th17 cell cultures.
Conclusions: Our study demonstrates that GPR68 activation can negatively regulate IL-22 production from human CD4 T cells in the presence of an AhR agonist. RNA-seq is a powerful method to identify novel gene targets that regulate cytokines involved in chronic inflammatory diseases.
Overall design Naïve CD4 T cells were purified from peripheral blood mononuclear cells isolated from six patient samples. Four experimental conditions were created for each sample: media only (control); Th17 differentiated; Th17+FICZ; and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. Differential gene expression analysis identified genes that were expressed at significantly different levels than the control (Media). Ingenuity pathway analysis revealed the most common cellular functions for genes regulated by each treatment.
Contributor(s) McAleer JP, Roar B, Fan J, Denvir J, Primerano DA
Citation(s) 30026493
NIH grant(s)
Grant ID Grant title Affiliation Name
Submission date Jul 31, 2017
Last update date May 15, 2019
Contact name James Denvir
Organization name Marshall University School of Medicine
Department Biochemistry and Microbiology
Lab Genomics and Bioinformatics Core Facility
Street address One John Marshall Drive
City Huntington
State/province WV
ZIP/Postal code 25755
Country USA
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (24)
GSM2722356 A-Media
GSM2722357 A-Th17
GSM2722358 A-Th17_CH223191
BioProject PRJNA396484
SRA SRP114371

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Supplementary file Size Download File type/resource
GSE102045_normalized_counts.csv.gz 1.4 Mb (ftp)(http) CSV 1.9 Kb (ftp)(http) TXT
GSE102045_raw_counts.csv.gz 451.3 Kb (ftp)(http) CSV
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