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Series GSE234134 Query DataSets for GSE234134
Status Public on Jun 07, 2023
Title Sex bias in autoimmunity is driven by androgen regulation of T cell-intrinsic mechanisms
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Major autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis, rheumatoid arthritis and Graves’ disease display a striking female bias, with a female-to-male incidence ratio ranging up to 9:1 in SLE. Sex hormones contribute to protection of males from autoimmunity, but precise molecular mechanisms of such protection are poorly understood. Here, we find that Androgen Receptor (AR), a nuclear receptor regulating a plethora of genes, is active in T cells during development and regulates directly genes involved in T cell activation or indirectly through regulation of other transcription factors. A gene encoding a phosphatase Ptpn22, a negative regulator of T cell receptor signaling, was found to be dependent of the presence of androgen receptor (AR) in males. Castration or deletion of AR reduced expression of Ptpn22. In a mouse model of Systemic Lupus Erythematosus (SLE), Ptpn22 deletion led to the loss of sexual dimorphism. Moreover, analysis of the regulatory regions of Ptpn22 gene revealed a highly conserved sequence that was necessary for upregulation of the gene’s expression by androgens. Mutation of this sequence in Non-Obese Diabetic (NOD) mice led to enhanced ability of T cells to cause Type 1 diabetes. Thus, PTPN22 is likely to participate in disease pathogenesis making it and other AR-regulated genes fair targets for therapeutic interventions in major autoimmune diseases.
Overall design AR ChIP-seq profiling of murine thymocytes
Contributor(s) Lee J, Yurkovetskiy L, Khan A, Chervonsky A
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Submission date Jun 05, 2023
Last update date Jun 09, 2023
Contact name Aly Azeem Khan
Organization name University of Chicago
Street address 6045 S. Kenwood Ave.
City Chicago
State/province IL
ZIP/Postal code 60637
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (3)
GSM7446572 Thymocytes,AR,Ab2
GSM7446573 Thymocytes,AR,Ab1
GSM7446574 Thymocytes,input
BioProject PRJNA980178

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE234134_RAW.tar 240.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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