|
Status |
Public on Jan 08, 2019 |
Title |
Blimp1 is required to repress Foxp3+ regulatory T cell pathogenic activity in mice |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
|
Summary |
Foxp3+Tregcells are essential modulators of immune responses but under specific conditions can acquire inflammatory properties and potentially contribute to disease pathogenesis. Here we show that the transcription factor Blimp1 is a critical regulator of Foxp3+Treg functional plasticity. The intrinsic expression of Blimp1 was required to prevent Treg from producing Th17-associated cytokines and acquiring an inflammatory phenotype while preserving Foxp3 expression. Mechanistically, Blimp1 acts as a direct repressor of the Il17a/Il17f genes in Foxp3+Treg and binding of Blimp1 at this locus is associated with altered chromatin status, reduced binding the co-activator p300, unaltered binding of the Th17-asssociated transcription factor RORt and more abundant binding of IRF4, which was required for the production of IL17A in Blimp1-deficient Foxp3+Tregcells, as shown by IRF4 siRNA-mediated knockdown. Consistent with their capacity to produce inflammatory cytokines, Blimp1-deficient Foxp3+Treg exacerbate Th17-mediated inflammation in vivo indicating that Blimp1 is required to prevent Treg cells from acquiring pathogenic properties
|
|
|
Overall design |
Total RNA from sorted Ctrl and Blimp1 CKO Foxp3 GFP+ pTreg cells
|
|
|
Contributor(s) |
Bankoti R, Ogawa C, Tang J, Brown J, Funari V, Martins GA |
Citation(s) |
28935958 |
Submission date |
Jul 26, 2016 |
Last update date |
Apr 09, 2019 |
Contact name |
Jie Tang |
E-mail(s) |
jie.tang@cshs.org
|
Organization name |
Cedars Sinai Medical Center
|
Street address |
8700 Beverly Blvd
|
City |
Los Angeles |
ZIP/Postal code |
90048 |
Country |
USA |
|
|
Platforms (1) |
GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
|
Samples (6)
|
|
Relations |
BioProject |
PRJNA335316 |