This SuperSeries is composed of the SubSeries listed below.
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression in response to Influenza A (PR8) infection
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression in response to Influenza A (PR8) infection
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression in response to Influenza A (PR8) infection
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View SamplesTo determine the role of the cytokine activin A in the regulation of human T follicular helper (Tfh) cell gene program, we performed a transcriptomic analysis (RNA-seq) of human naïve CD4 T cells differentiated in vitro with activin A. The analysis of the gene expression profile driven by activin A, alone or in combination with IL-12 (a know regulator of human Tfh differentiation/function), revealed that activin A can regulate the expression of multiple molecules involved in the differentiation and/or function of human Tfh cells. Overall design: Human naïve CD4 T cells were isolated from fresh PBMCs of healthy control subjects by magnetic bead isolation. Purity was measured by FACS as percentage of CD4+CD45RA+ cells and was 95% or higher. Upon isolation, naïve CD4 T cells were stimulated with anti-CD3/CD28 coated beads in the presence of the following cytokine combinations: no exogenous cytokines (beads only), activin A, IL-12, activin A+IL-12, TGFb, TGFb +IL12. Following 5 days of in vitro culture, live CD4 T cells were FACS sorted and gene expression was analyzed by RNA-seq. Data are from independent donors.
Activin A programs the differentiation of human TFH cells.
No sample metadata fields
View SamplesCD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation.
Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150).
Specimen part
View SamplesCD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation.
Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150).
No sample metadata fields
View SamplesComparison of transcriptome between GFP-RV+ Th1 cells and Lef1-RV+ Th1 cells Overall design: B6 mice received GFP-RV+ or Lef1-RV+ LCMV gp specific TCRtg Smarta cells and were infected with LCMV. On four days after infection, splenocytes were collected to sort CXCR5- Th1 cells per genotype. Contributor: LIAI RNAi Center (LIAI)
LEF-1 and TCF-1 orchestrate T(FH) differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6.
No sample metadata fields
View SamplesT cell receptor (TCR) stimulation of naïve CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naïve cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 controls de novo access to memory CTL-specific cistromes prior to the first cell division, and is essential for memory CTL differentiation. Runx3 specifically promotes accessibility of cis-acting regions highly enriched with IRF, bZIP and Prdm1-like family TF motifs, upregulates IRF4 and establishes feed-forward transcriptional circuits that induce fundamental CTL attributes in memory precursor cells. Runx3 drives uncoupling from the naïve cell state, but subsequently restrains terminal differentiation of nascent CTL by preventing high expression of the TF T-bet and slowing effector cell proliferation. Enforced Runx3 expression enhances memory CTL differentiation and increases their numbers during iterative infections. Thus, Runx3 functions in a pioneering role to initialize and then ensure memory CTL differentiate. Overall design: 6 samples, 2 replicates each, 2 wildtype controls
The Transcription Factor Runx3 Establishes Chromatin Accessibility of cis-Regulatory Landscapes that Drive Memory Cytotoxic T Lymphocyte Formation.
Cell line, Subject
View SamplesAnalysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection. A paper including data analysis of these experiments has been accepted for publication (Robert J. Johnston et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of follicular helper CD4 T cell differentiation).
Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.
Specimen part
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