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ATAC-seq profiling of in vitro FRC-conditioned, IL6-conditioned or control (anti-CD3/CD28)-stimulated CD8+ T cells

ABSTRACT: To broadly assess which pathways FRCs regulate in CD8+ T cells, we sorted CD8+ T cells for ATAC-seq following activation in whole splenocyte mixtures via soluble anti-CD3/CD28 (0.25μg/ml) for 48 hours (Stim), activated with anti-CD3/CD28 in the presence of Nos2–/– FRCs (FRC) or activated with anti-CD3/CD28 plus 100 ng/ml recombinant IL-6 (IL-6). Here we demonstrate that FRC-derived signals, including IL-6, act in concert with TCR signaling and co-stimulation to remodel chromatin and render essential transcription factor binding motifs accessible in activated CD8+ T cells. Signals from FRCs led to increased binding regions for MYC, HIF-1α and HIF-1β, which are known to promote metabolic pathways following T cell activation. Additionally, FRC-derived signals promoted activity of transcription factors that regulate survival and memory programs in T lymphocytes such as BATF and BACH2.

ORGANISM(S): Mus musculus

PROVIDER: GSE136903 | GEO | 2019/10/14

REPOSITORIES: GEO

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RNA-seq profiling of in vitro FRC-conditioned, IL6-conditioned or control (anti-CD3/CD28)-stimulated CD8+ T cells

Project description:To broadly assess which pathways FRCs regulate in CD8+ T cells, we sorted CD8+ T cells for RNA-seq following activation in whole splenocyte mixtures via soluble anti-CD3/CD28 for 48 hours (Stim), activated with anti-CD3/CD28 in the presence of Nos2–/– FRCs (FRC) or activated with anti-CD3/CD28 plus 100 ng/ml recombinant IL-6 (IL-6). Here we demonstrate that FRC-derived signals, including IL-6, act in concert with TCR signaling and co-stimulation to promote the expression of MYC and HIF-1-dependent glycolytic genes and vital pro-survival genes (encoding BCL-2 family members, inhibitors of apoptosis [IAPs] members and Cflar) in activated CD8+ T cells.

2019-10-14 | GSE136898 | GEO

In vitro FRC-conditioned, IL6-conditioned or control (anti-CD3/CD28)-stimulated CD8+ T cells

Project description:In vitro FRC-conditioned, IL6-conditioned or control (anti-CD3/CD28)-stimulated CD8+ T cells

| PRJNA564011 | ENA

Microarray profiling of in vitro expanded FRCs cultured alone or with activated T cells

Project description:To investigate whether FRCs express molecules capable of promoting the functions of activated T cells, we expanded FRCs from primary lymph node stromal cell (LNSC) cultures as previously described (Lukacs-Kornek et al., Nature Immunology, 2011), and then cultured them alone or with splenocytes activated with soluble antibody (0.25μg/ml) against CD3 (anti-CD3) and anti-CD28 for 16 hours. FRCs co-cultured with activated T cells upregulated expression of genes encoding molecules known to dampen T cell function such as Arg1, CD274 and Nos2. However, in response to activated T cells, FRCs also upregulated molecules with immunostimulatory capabilities such as Icosl, Cd40 and Il6.

2019-09-06 | GSE136958 | GEO

Genome wide expression profiles (RNAseq) of human CD8+ T cells in resting, activated (CD3+CD28) and PD-1-stimulated cells (CD3+CD28+PD-L1-Fc) at diferent time points

Project description:Background: Binding of the programmed death-1 (PD-1) receptor to its ligands (PD-L1/2) transduces inhibitory signals that promote exhaustion of activated T cells. Blockade of the PD 1 pathway is widely used for cancer treatment, yet the inhibitory signals transduced by PD-1 in T cells remain elusive. Methods: Expression profiles of human CD8+ T cells in resting, activated (CD3+CD28) and PD-1-stimulated cells (CD3+CD28+PD-L1-Fc) conditions were evaluated by RNA-seq. Bioinformatic analyses were used to identify signaling pathways differentially regulated in PD 1-stimulated cells.

2019-05-29 | GSE122149 | GEO

The effect of IFNα on human CD8 T cells_with other concomitant signals

Project description:IFN alpha mediated gene expression pattern. The effect of IFN alpha on human CD8 T cells responding to antigen (signal 1) and costimulatory signals (signal 2) provided by beads coated with anti-CD3 and anti-CD28 mAbs. This analysis examined the effects of IFN alpha on human CD8 T cells responding to antigen (signal 1) and costimulatory signals (signal 2) provided by beads coated with anti-CD3 and anti-CD28 mAbs. Magnetically sorted untouched CD8+CD45R0- T cells from three different donors were unstimulated or stimulated with IFNa2b or with anti-CD3/CD28 Beads alone or along with IFNa2b or IFNa5 for 48 hours. Individual mRNA samples were analyzed using HG-U133A 2.0 array gene chips. Keywords: Gene expression analysis after different stimulation Magnetically sorted untouched CD8+CD45R0-T cells from three different donors (named A, B and C) unstimulated or stimulated with IFN alpha 2b or with anti-CD3/CD28 beads alone or along with IFN alpha 2b or IFN alpha 5 for 48 hours.

2010-07-23 | E-GEOD-17301 | biostudies-arrayexpress

RNA-seq profiling of in vitro FRC-conditioned, IL6-conditioned or control (anti-CD3/CD28)-stimulated CD8+ T cells

Project description:RNA-seq profiling of in vitro FRC-conditioned, IL6-conditioned or control (anti-CD3/CD28)-stimulated CD8+ T cells

| PRJNA564009 | ENA

ATAC-seq profiling of in vitro FRC-conditioned, IL6-conditioned or control (anti-CD3/CD28)-stimulated CD8+ T cells

Project description:ATAC-seq profiling of in vitro FRC-conditioned, IL6-conditioned or control (anti-CD3/CD28)-stimulated CD8+ T cells

| PRJNA564015 | ENA

Fibroblastic reticular cell lineage convergence in Peyer’s patches governs intestinal homeostasis

Project description:Peyer`s patches (PP) are underpinned by a dense network of FRCs. To elaborate the subset composition and topological organization of PP FRCs, we employed well-characterized Ccl19-Cre and Col6a1-Cre mouse models that permit FRC targeting in secondary lymphoid organs. To define PP FRC subsets and their relation to the observed FRC lineages, we isolated fibroblasts from Col6a1Eyfp and Ccl19Eyfp PPs and performed droplet-based single cell transcriptomics analysis. Taken together, the molecular definition of the PP FRC landscape reveals two FRC lineages furnishing distinct microenvironmental niches.

2021-01-22 | E-MTAB-9162 | biostudies-arrayexpress

The effect of IFNα on human CD8 T cells_with other concomitant signals

2010-07-23 | GSE17301 | GEO

Fibroblastic reticular cells serve as primary immune checkpoint in visceral adipose tissues and secure peritoneal immunity

Project description:Immune protection of the body cavities depends on the swift activation of innate and adaptive immune responses in non-classical secondary lymphoid organs known as fat-associated lymphoid clusters (FALCs). While it is well-established that fibroblastic reticular cells (FRCs) are an integral component of the immune-stimulating infrastructure of lymph nodes and other classical secondary lymphoid organs, it has remained elusive whether and how FRCs in FALCs contribute to peritoneal immunity. Using FRC-specific gene targeting, we found that FALCs are underpinned by an elaborated FRC network and that initiation of peritoneal immunity was governed through FRC activation via MyD88-dependent innate immunological sensing. FRC-specific ablation of Myd88 expression blocked recruitment of inflammatory monocytes into FALCs and subsequent CD4+ T cell-dependent B-cell activation. Moreover, containment of Salmonella infection was compromised in conditionally Myd88-deficient mice indicating that FRCs in FALCs function as initial checkpoint in the orchestration of protective immune responses in the peritoneal cavity.

2018-06-12 | E-MTAB-6886 | biostudies-arrayexpress

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