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Series GSE121703 Query DataSets for GSE121703
Status Public on Oct 18, 2019
Title The X chromosome gene Kdm6a modulates multiple immune response genes in CD4+ T cells and is disease promoting in autoimmune disease
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Multiple sclerosis (MS) is a T-cell mediated autoimmune disease that has a sexually dimorphic pattern in disease susceptibility. Consistent with many autoimmune diseases, females are more susceptible than males to MS. Sexual dimorphisms may be due to differences in sex hormones, sex chromosome genes, or both. Regarding sex chromosome genes, a small percentage of X chromosome genes escape the dosage compensation mechanism of X inactivation and have higher expression in females (XX) compared to males (XY). According to the high throughput analysis, the top sexually dimorphic gene with higher expression in CD4+ T cells from females (vs. males) and from XX mice (vs. XY) was Kdm6a, a histone demethylase and transcription factor on the X chromosome. Deletion of Kdm6a specifically in CD4+ T cells ameliorated clinical disease and reduced neuropathology in the classic CD4+ T cell mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). Global transcriptome analysis in CD4+ T cells from EAE mice with a specific deletion of Kdm6a showed upregulation of Th2 and Th1 activation pathways and downregulation of neuroinflammation signaling pathways. Together, this demonstrates that the X escapee Kdm6a regulates multiple immune response genes, providing a mechanism for sex differences in autoimmune disease susceptibility.
Overall design To determine the influence of differential Kdm6a expression in immune responses, we induced EAE in cKO mice (Kdm6a gene is conditionally knocked out in CD4 cells) and their WT littermate controls. On EAE day 17, lymph node cells were isolated and cultured with autoantigen (MOG35-55) before CD4+ T cell sorting. Whole transcriptome analysis for CD4+ T cells from WT and cKO EAE mice were performed using RNA-Seq.
Contributor(s) Itoh Y, Itoh N, Golden L, Arnold AP, Voskuhl R
Citation(s) 31403472
Submission date Oct 23, 2018
Last update date Jan 17, 2020
Contact name Yuichiro Itoh
Phone 3102068999
Organization name UCLA
Department Neurology
Street address 635 Charles E. Young Drive South
City Los Angeles
State/province California
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (7)
GSM3444250 KO2
GSM3444251 KO3
GSM3444252 KO7
BioProject PRJNA498118
SRA SRP166658

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Supplementary file Size Download File type/resource
GSE121703_Kdm6a.CD4_rawcounts.xlsx 1.7 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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