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Series GSE121764 Query DataSets for GSE121764
Status Public on Oct 26, 2018
Title Blimp1 maintains regulatory T cell identity at sites of inflammation through epigenetic imprinting
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. We here establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway was dependent on the transcriptional regulator Blimp1, which prevented dismantling of Foxp3 expression and "toxic" gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulated IL-6- and STAT3-mediated methylation of Treg cell-specific conserved non-coding sequence 2 (CNS2) in the Foxp3 locus. Consequently, CNS2 was heavily methylated when Blimp1 was ablated, leading to loss of Foxp3 expression and severe disease. These findings identify a Blimp1-dependent epigenetic pathway that preserves Treg cell stability in inflamed non-lymphoid tissues.
Overall design Comparison of DNA accessibility by Omni-ATAC-seq in conventional T cells (Tconv) and regulatory T cells (Treg) of wild-type vs Treg conditional Blimp1 deficient mice isolated from the CNS and spleen at the peak of experimental autoimmune encephalitis (EAE). All samples were FACS sorted ex vivo according to CD4+Foxp3(GFP)- = Tconv and CD4+Foxp3(GFP)+ = Treg from mixed bone morrow chimeras with congenically marked wild-type (CD45.1) and Treg conditional Blimp1 KO compartments (CD45.2).
Contributor(s) Korn T, Garg G, Lepennetier G, Schotta G, Domínguez Moreno H
Citation(s) 30759395
Submission date Oct 25, 2018
Last update date Mar 12, 2019
Contact name Thomas Korn
Phone 00498941405617
Organization name Technical University of Munich
Department Neurology
Lab Korn lab
Street address Ismaninger Str. 22
City Munich
State/province Bavaria
ZIP/Postal code 81675
Country Germany
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (17)
GSM3445822 GS516_Spleen1.1_WT_Tconv_ATAC
GSM3445823 GS520_Spleen2.1_WT_Tconv_ATAC
GSM3445824 GS523_Spleen3.1_WT_Tconv_ATAC
BioProject PRJNA498396
SRA SRP166840

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Supplementary file Size Download File type/resource
GSE121764_RAW.tar 1.4 Gb (http)(custom) TAR (of BIGWIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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