Genomics

Dataset Information

302

Interleukin-23-induced transcription factor Blimp1 promotes pathogenicity of T helper 17 cells


ABSTRACT: Interleukin-23 (IL-23) is a pro-inflammatory cytokine required for the pathogenicity of T helper 17 (Th17) cells but the molecular mechanisms governing this process remain unclear. We identified the transcription factor Blimp-1 (Prdm1) as a key IL-23-induced factor that drove the inflammatory function of Th17 cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced Th17 activation and reduced severity of autoimmune encephalomyelitis. Furthermore, genome wide occupancy and overexpression studies in Th17 cells revealed that Blimp-1 co-localized with transcription factors RORγt, STAT-3 and p300 at the Il23r, Il17a/f and Csf2 cytokine loci to enhance their expression. Blimp-1 also directly bound to and repressed cytokine loci Il2 and Bcl6. Taken together, our results demonstrate that Blimp-1 is an essential transcription factor downstream of IL-23 that acts in concert with RORγt to activate the Th17 inflammatory program. Genome-wide binding analysis of Blimp1 from in vitro generated T effector and regulatory cells

ORGANISM(S): Mus musculus  

SUBMITTER: B Joyce   G Vahedi  M J McGeachy  Y Kanno  K Hirahara  S Sadekova  T McClanahan  W M Blumenschein  C J Haines  Y Chen  J J O'Shea  D J Cua  S Sukumar  R Jain  Yuka Kanno 

PROVIDER: E-GEOD-75724 | ArrayExpress | 2016-06-15

SECONDARY ACCESSION(S): GSE75724SRP067078PRJNA305162

REPOSITORIES: GEO, ArrayExpress, ENA

altmetric image

Publications


Interleukin-23 (IL-23) is a pro-inflammatory cytokine required for the pathogenicity of T helper 17 (Th17) cells but the molecular mechanisms governing this process remain unclear. We identified the transcription factor Blimp-1 (Prdm1) as a key IL-23-induced factor that drove the inflammatory function of Th17 cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced  ...[more]

Similar Datasets

2010-08-31 | GSE23681 | GEO
2010-08-31 | GSE23505 | GEO
2010-08-31 | E-GEOD-23681 | ArrayExpress
2010-08-31 | E-GEOD-23505 | ArrayExpress
2011-02-09 | E-GEOD-26552 | ArrayExpress
2011-02-09 | GSE26551 | GEO
2013-10-30 | E-GEOD-43409 | ArrayExpress
2011-02-09 | E-GEOD-26551 | ArrayExpress
| GSE122624 | GEO
2011-03-28 | GSE27241 | GEO