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| 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
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| 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.
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| 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).
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| Contributor(s) |
Korn T, Garg G, Lepennetier G, Schotta G, DomÃnguez Moreno H |
| Citation(s) |
30759395 |
| Submission date |
Oct 25, 2018 |
| Last update date |
Mar 12, 2019 |
| Contact name |
Thomas Korn |
| E-mail(s) |
thomas.korn@me.com
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| Phone |
00498941405617
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| Organization name |
Technical University of Munich
|
| Department |
Neurology
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| Lab |
Korn lab
|
| Street address |
Ismaninger Str. 22
|
| City |
Munich |
| State/province |
Bavaria |
| ZIP/Postal code |
81675 |
| Country |
Germany |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA498396 |
| SRA |
SRP166840 |
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