Continued Bcl6 expression prevents the transdifferentiation of established Tfh cells into Th1 cells during acute viral infection
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ABSTRACT:
PROVIDER: PRJNA596262 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10724662_1.fastq.gz | Fastqsanger.gz | |||
| SRR10724662_2.fastq.gz | Fastqsanger.gz | |||
| SRR10724663_1.fastq.gz | Fastqsanger.gz | |||
| SRR10724663_2.fastq.gz | Fastqsanger.gz | |||
| SRR10724664_1.fastq.gz | Fastqsanger.gz |
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Project description:By using a temporally-controlled system for the ablation of Bcl6 and Cxcr5 speficially in CD4 T cells, the requirements of both factors for the maintenance of Tfh cells were investigated
2020-10-06 | GSE142229 | GEO
Project description:We found that a number of Tfh cells downmodulated BCL6 protein after their development, and we sought to compare the gene expression between BCL6-hi Tfh cells and BCL6-low Tfh cells.
2011-06-02 | GSE24574 | GEO
Project description:We found that a number of Tfh cells downmodulated BCL6 protein after their development, and we sought to compare the gene expression between BCL6-hi Tfh cells and BCL6-low Tfh cells. CD4+ T cells were sorted from immunized and non-immunized mice for RNA extraction and hybridization on Affymetrix microarrays. Bcl6yfp/+ OT-II cells were transferred to congenic recipient mice, and immunized with NP-OVA in CFA subcutaneously. Seven or ten days after immunization, cells were collected from draining lymph nodes, and sorted on FACSAria by the expression of CXCR5, PD-1 and BCL6-YFP. Naive CD4+ T cells were CD4+ CD44lo CD62Lhi cells from unimmunized mice.
2011-06-02 | E-GEOD-24574 | biostudies-arrayexpress
Project description:Tfh cells are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of Bcl6 in Tfh have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells. BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration and repression of alternative cell fates. Interestingly, although some BCL6 bound genes possessed BCL6 DNA binding motifs, many BCL6-bound loci were instead characterized by the presence of DNA motifs for AP1 or STAT. AP1 complexes are key positive downstream mediators of TCR signaling and external stimuli. We show that BCL6 can directly bind AP1, and BCL6 depends on AP1 for recruitment to BCL6 binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity. These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology, and provide insight into how this master regulator mediates distinct cell-context dependent phenotypes. Sorted naM-CM-/ve tonsil cells were activated with anti-CD3+CD28 Ab coated beads and transduced with BCL6 or control lentiviral vectors as described. RNA was isolated at day 5 following LV infection and microarrays performed as discussed herein. RNA was isolated with the RNeasy Micro Kit (QIAGEN). The quantity and quality of the RNA were confirmed with a NanoDrop 2000c (Thermo Fisher Scientific) and an Experion Electrophoresis System (Bio-Rad). Samples (20 ng) were amplified with Illumina MessageAmp II aRNA Amplification Kits (Ambion), hybridized to HumanHT-12_V4 BeadChips (Illumina), and quantified with Genome Studio (Illumina). Normalized data (heatmap of blood cells) or raw data (heatmap of tonsil cells and Volcano plot) were analyzed with the GenePattern software suite.
2015-03-01 | E-GEOD-66373 | biostudies-arrayexpress
Project description:Tfh cells are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of Bcl6 in Tfh have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells. BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration and repression of alternative cell fates. Interestingly, although some BCL6 bound genes possessed BCL6 DNA binding motifs, many BCL6-bound loci were instead characterized by the presence of DNA motifs for AP1 or STAT. AP1 complexes are key positive downstream mediators of TCR signaling and external stimuli. We show that BCL6 can directly bind AP1, and BCL6 depends on AP1 for recruitment to BCL6 binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity. These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology, and provide insight into how this master regulator mediates distinct cell-context dependent phenotypes.
2015-03-01 | GSE66373 | GEO
Project description:Tfh cells are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of Bcl6 in Tfh have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells. BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration, TCR signaling, and repression of alternative cell fates. Interestingly, although some BCL6 bound genes possessed BCL6 DNA binding motifs, many BCL6-bound loci were instead characterized by the presence of DNA motifs for AP1 or STAT. AP1 complexes are key positive downstream mediators of TCR signaling and external stimuli. We show that BCL6 can directly bind AP1, and AP1 and BCL6 co-occupied BCL6 binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity. These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology, and provide insight into how this master regulator mediates distinct cell-context dependent phenotypes.
2015-03-20 | GSE59933 | GEO
Project description:We analyzed the transcriptome differences of BCL6-sufficient (CD4-Cre) and -insufficient (CD4-CrexBcl6fl/+) OT-II TFH cells. CD4-CrexBcl6fl/+ or control CD4-Cre OT-II T cells were transferred into CD45.1 Sap-/- mice. At day 3 post NP-OVA immunization, CXCR5hiPD-1hi TFH cells were sort-purified from the draining lymph node and prepared for RNA-seq analysis. Two technical repeats of ~200 cells per sample from each of 3 mice were included. BCL6-insufficient TFH cells differentially expressed many genes; among those downregulated were Stim1 and Plcg1, which code for STIM1 and PLCg1, respectively, that both impinge on calcium signaling downstream of TCR activation. Moreover, KEGG pathway analyses revealed that the calcium signaling-related pathway was generally upregulated in wildtype as compared to BCL6-insufficient TFH cells. These data support the notion that BCL6 control follicular T-B interactions by regulating multiple target genes involved in antigen-triggered calcium signaling in T cells.
2021-07-30 | GSE180924 | GEO
Project description:T follicular helper (Tfh) cell is a unique T cell subset specialized in promoting germinal center reactions. Bcl6 has been identified as an obligatory transcription factor in Tfh cells; however, the molecular mechanism underlying Bcl6 function still remains unknown. Here, we combined genome-wide Bcl6 occupancy and transcriptome profiling to systemically analyze Bcl6 targets in Tfh cells. We found that Bcl6 exhibits unique binding preferences in Tfh cells from those in Th9, B cells and macrophage and its binding is closely associated with decrease in 5-hydroxymethylcytosine (5hmC). Importantly, Bcl6 directly binds to the IL-7R/CD127 gene and suppresses its expression. Bcl6 also binds the same sequences recognized by signal transducer and activator of transcription (STAT) 5, downstream of IL-7R. Bcl6 promotes CD127loPDhi Tfh cell differentiation; deletion of the Bcl6 gene in T cells results in enhanced IL-7R-STAT5 signaling and substantial expansion of CD127hiPDlo non-Tfh cells. Our study thus systemically examines Bcl6-controlled regulatory networks and provides novel insights into its biological functions in Tfh cells.
2016-01-31 | GSE72188 | GEO
Project description:To understand physiological characteristics of CD4+CD8+ Double-positive (DP)-Tfh cells, we continued to conduct comparative transcriptome analysis of tonsillar Tfh cell populations, including DP-Tfh cells and CD4+CD8- single-positive (SP)-Tfh cells as a control. Results showed that DP-Tfh cells preferentially expressed transcripts related to CTLs, such as CD8 (CD8A and CD8B), Eomes, and granzymes, suggesting a possible cytotoxic attribute of DP-Tfh cells. Th1-cell related signature genes were also presented in DP-Tfh cells and cytokines like interferon (IFN)-gamma and interleukin (IL)-10 were found to be highly presented in DP-Tfh cells rather than SP-Tfh cells. Of note, the expression profile of authentic Tfh-cell (i.e. SP-Tfh cell) related genes like IL-4, IL-21, Bcl6, and Pou2af1 seemed to be shared with DP-Tfh cells.
2022-08-10 | GSE202616 | GEO
Project description:T Follicular helper (Tfh) cell is an effector CD4+ T cell subset specialized in helping B cells in germinal centers (GC) reactions. Although Bcl6 was identified as a Tfh-specific transcription factor essential for their development, the molecular mechanisms underlying Bcl6 regulation and Tfh cell commitment remain unclear. Here, we report that Tox2 transcription factor is highly expressed in Tfh cells, regulated by Bcl6 and STAT3. Forced expression of Tox2 drives Bcl6 expression and Tfh development. Mechanistically, Tox2 directly binds to Tfh-associated genes, including Bcl6, and functions to promote their chromatin accessibility and modulate the activities of other Tfh-regulating factors. Conversely, genetic deletion of Tox2 results in defective Tfh differentiation, and inhibiting both Tox and Tox2 in T cells abolishes Tfh differentiation and GC response. Thus, our results demonstrate that Tox2 is a key transcription factor that regulates Bcl6 expression and Tfh development and suggest a Tox2-Bcl6 axis in feed-forward regulation of Tfh program.
2019-10-30 | GSE136539 | GEO