RNA-seq of CD4+ T cell subsets in KLH-gp61 immunization
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE137122 | GEO | 2020/05/03
REPOSITORIES: GEO
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Project description:T follicular helper (TFH) cells are a distinct type of CD4 T cells that are essential for most antibody and B lymphocyte responses. TFH regulation and dysregulation is involved in a range of diseases. Bcl6 is the lineage defining transcription factor of TFH cells and its activity is essential for TFH cell differentiation and function. However, how Bcl6 controls TFH biology has largely remained unclear, at least in part due to intrinsic challenges of connecting repressors to gene upregulation in complex cell types with multiple possible differentiation fates. Multiple competing models were tested here by a series of experimental approaches to determine that Bcl6 exhibits negative autoregulation and controls pleiotropic attributes of TFH differentiation and function (migration, costimulation, inhibitory receptors, and cytokines) via multiple repressor-of-repressor gene circuits.
2020-05-03 | GSE137383 | GEO
Project description:T follicular helper (TFH) cells are a distinct type of CD4 T cells that are essential for most antibody and B lymphocyte responses. TFH regulation and dysregulation is involved in a range of diseases. Bcl6 is the lineage defining transcription factor of TFH cells and its activity is essential for TFH cell differentiation and function. However, how Bcl6 controls TFH biology has largely remained unclear, at least in part due to intrinsic challenges of connecting repressors to gene upregulation in complex cell types with multiple possible differentiation fates. Multiple competing models were tested here by a series of experimental approaches to determine that Bcl6 exhibits negative autoregulation and controls pleiotropic attributes of TFH differentiation and function (migration, costimulation, inhibitory receptors, and cytokines) via multiple repressor-of-repressor gene circuits.
2020-05-03 | GSE137121 | GEO
Project description:Here, using ChIP-seq, we demonstrate that the transcriptional repressor Adenovirus E4 promoter-binding protein (E4BP4) binds directly to the Bcl6 promoter, which a key transcription factor controlling Tfh cell differentiation. By obtaining sequence from chromatin immunoprecipitated DNA of E4BP4 overexpressing CD4+T cells, we generated genome-wide binding gene spectrums of E4BP4. These results reveal that E4BP4 interacts with BCL6 and E4BP4 directly modulated the expression of Bcl6 to reveal the mechanism downstream of E4BP4 that regulates Tfh cell differentiation.
2021-01-19 | GSE121387 | GEO
Project description:BCL6 orchestrates Tfh differentiation via multiple distinct mechanisms
| PRJNA276674 | ENA
Project description:BCL6 orchestrates Tfh differentiation via multiple distinct mechanisms
| PRJNA257089 | ENA
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:Follicular helper T (Tfh) are a subset of CD4+ T helper cells that provide help to germinal center B cells and mediate the development of long-lived humoral immunity. Tfh cells dysregulation is associated with several major autoimmune diseases. Although recent studies showed Tfh cells differentiation is controlled by the transcription factor Bcl6, cytokines and cell-cell signals, limited information is available on the proteome and post-translational modifications (PTM) of proteins in human Tfh cells. In this study, using TMT labeling technique, antibody-based affinity enrichment and high-resolution LC-MS/MS analysis, we investigated quantitative proteome and acetylome in human naive CD4+ T cells and in vitro induced Tfh (iTfh) cells. In total, we identified 802 up-regulated proteins and 598 down-regulated proteins at the threshold of 1.5 folds in iTfh cells compared to naive CD4+ T cells. With the aid of intensive bioinformatics, biological process, cellular compartment, molecular function, KEGG pathway and protein-protein interaction of these differentially expressed proteins were revealed. Moreover, our acetylome data showed that 22 lysine acetylated proteins are up-regulated and 26 lysine acetylated proteins are down-regulated in iTfh cells compared to the naive CD4+ T cells, among which 11 differentially acetylated lysine residues in core histone were identified, indicating proteins acetylation and epigenetic mechanism are involved in regulating Tfh cells differentiation. These data provide a significant resource for studies of Tfh differentiation and normal and perturbed Tfh cell function.
2021-03-19 | PXD008563 | Pride
Project description:CD4+ T follicular helper cells (TFH) are critical for the formation and function of B cell responses to infection or immunization, but also play an important role in autoimmunity. The factors that contribute to the differentiation of this helper cell subset are incompletely understood, although several cytokines including IL-6, IL-21 and IL-12 can promote TFH cell formation. Yet, none of these factors, nor their downstream cognate STATs, have emerged as non-redundant, essential drivers of TFH cells. This suggests a model in which multiple factors can contribute to the phenotypic characteristics of TFH cells. As type I interferons (IFNs) are often generated in immune responses, we set out to investigate if these factors are relevant to TFH cell differentiation. Type I IFNs promote Th1 responses, thus one possibility was these factors antagonized TFH-expressed genes. However, we show that type I IFNs (IFN-α/β) induced Bcl6 expression, the master regulator transcription factor for TFH cells, and CXCR5 and PD-1 (encoded by Pdcd1), key surface molecules expressed by TFH cells. In contrast, type I IFNs failed to induce IL-21, the signature cytokine for TFH cells. The induction of Bcl6 was regulated directly by STAT1, which bound to the Bcl6, Cxcr5 and Pdcd1 loci. These data suggest that type I IFNs (IFN-α/β) and STAT1 can contribute to some features of TFH cells but are inadequate in inducing complete programming of this subset. The role of STAT1 in type I interferon treated CD4+ T cells was investigated by Chip-seq of STAT1.
2014-01-22 | E-GEOD-51531 | biostudies-arrayexpress