Foxp3+ regulatory T cells (Treg) are essential modulators of immune responses, but the molecular mechanisms underlying their function are not fully understood. Here we show that the transcription factor Blimp-1 is a crucial regulator of the Foxp3+RORγt+ Treg subset. The intrinsic expression of Blimp-1 in these cells is required to prevent production of Th17-associated cytokines. Direct binding of Blimp-1 to the Il17 locus in Treg is associated with inhibitory histone modifications but unaltered binding of RORγt. In the absence of Blimp-1, the Il17 locus is activated, with increased occupancy of the co-activator p300 and abundant binding of the transcriptional regulator IRF4, which is required, along with RORγt, for IL-17 expression in the absence of Blimp-1. We also show that despite their sustained expression of Foxp3, Blimp-1-/- RORγt+IL-17-producing Treg lose suppressor function and can promote intestinal inflammation, indicating that repression of Th17-associated cytokines by Blimp-1 is a crucial requirement for RORγt+ Treg function.
Pubmed ID: 30282028 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsCollection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsCommercial supplier and developer of in vivo antibodies. Provides antibodies and antibody production services.
View all literature mentionsWeb tool for analyzing regulatory potential of noncoding sequences. rVISTA web server is interconnected with TRANSFAC database, allowing users to either search for matrices present in TRANSFAC library collection or search for user defined consensus sequences. rVISTA 2.0 web server is used for high throughput discovery of cis-regulatory elements. Can process alignments generated by zPicture and blastz alignment programs or use pre-computed pairwise alignments of several vertebrate genomes available from ECR Browser and GALA database. Evolutionary analysis of transcription factor binding sites.
View all literature mentionsMus musculus with name C57BL/6-Foxp3tm1Flv/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6-Il17atm1Bcgen/J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Il10tm1Cgn/J from IMSR.
View all literature mentionsMus musculus with name B6.129(Cg)-Foxp3tm4(YFP/icre)Ayr/J from IMSR.
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis unknown targets normal rabbit IgG
View all literature mentionsThis polyclonal targets RORC
View all literature mentionsThis polyclonal targets Histone H3, trimethyl (Lys27)
View all literature mentionsThis polyclonal targets Histone H3 (tri methyl K4)
View all literature mentionsThis monoclonal targets IL-4
View all literature mentionsThis monoclonal targets IFNγ
View all literature mentionsThis monoclonal targets CD28
View all literature mentionsThis monoclonal targets CD3ε
View all literature mentionsThis polyclonal targets GFP Fluorescein
View all literature mentionsThis monoclonal targets Mouse RORγt
View all literature mentionsThis monoclonal targets ROR gamma (t)
View all literature mentionsThis monoclonal targets CD103 (Integrin alpha E)
View all literature mentionsThis monoclonal targets IRF4
View all literature mentionsThis monoclonal targets IL-10
View all literature mentionsThis monoclonal targets HELIOS
View all literature mentionsThis monoclonal targets FOXP3
View all literature mentionsThis monoclonal targets FOXP3
View all literature mentionsThis monoclonal targets CD25
View all literature mentionsThis monoclonal targets IFN-gamma
View all literature mentionsThis monoclonal targets IL-17F
View all literature mentionsThis monoclonal targets IL-17A
View all literature mentionsThis monoclonal targets IL-17A
View all literature mentionsThis monoclonal targets IL-17A
View all literature mentionsThis monoclonal targets CD278
View all literature mentionsThis monoclonal targets CD62L
View all literature mentionsThis monoclonal targets CD44
View all literature mentionsThis monoclonal targets CD44
View all literature mentionsThis monoclonal targets CD44
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets TCR beta chain
View all literature mentionsThis monoclonal targets TCR beta chain
View all literature mentionsThis monoclonal targets CD4
View all literature mentions