Regulation of Tfh differentiation by PDK1
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE154976 | GEO | 2021/02/15
REPOSITORIES: GEO
Similar Datasets
Project description:Regulation of Tfh differentiation by PDK1
| PRJNA648089 | ENA
Project description:CD4 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. Analysis of in vivo polyclonal GC Tfh vs Tfh vs Non-Tfh eight days after LCMV viral infection. Analysis of in vivo follicular helper CD4 T cells (CXCR5high GL7low), versus germinal center follicular helper CD4 T cells (CXCR5hi GL7hi), versus non-follicular helper CD4 T cells (CXCR5low) eight days after viral infection.
2010-04-28 | E-GEOD-21380 | biostudies-arrayexpress
Project description:T follicular helper (Tfh) cells are a specialized subset of CD4 T cells that are essential for most antibody productions and humoral responses. It is well characterized that transcriptional network exerts indispensable roles in Tfh cell differentiation. However, how post-transcriptional regulation controls Tfh biology has largely remained unclear. Multiple mice models were used here by a series of experimental approaches to illustrate m6A methyltransferase Mettl3 programs Tfh cell differentiation at post-transcriptional layer.
2021-01-19 | GSE129648 | GEO
Project description:CD4 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. Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) WT and Sh2d1a-/- follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.
2010-04-28 | E-GEOD-21379 | biostudies-arrayexpress
Project description:Leber2016 - Expanded model of Tfh-Tfr
differentiation - Helicobacter pylori infection
The parameters used in the model were
obtained from experiments conducted by the authors, previous
publications [
1,
2,
3] and
parameter optimisation carried out in the paper using particle
swarm and genetic algorithms.
This model is described in the article:
Bistability analyses of CD4+
T follicular helper and regulatory cells during Helicobacter
pylori infection.
Leber A, Abedi V, Hontecillas R,
Viladomiu M, Hoops S, Ciupe S, Caughman J, Andrew T,
Bassaganya-Riera J.
J. Theor. Biol. 2016 Jun; 398:
74-84
Abstract:
T follicular helper (Tfh) cells are a highly plastic subset
of CD4+ T cells specialized in providing B cell help and
promoting inflammatory and effector responses during infectious
and immune-mediate diseases. Helicobacter pylori is the
dominant member of the gastric microbiota and exerts both
beneficial and harmful effects on the host. Chronic
inflammation in the context of H. pylori has been linked to an
upregulation in T helper (Th)1 and Th17 CD4+ T cell phenotypes,
controlled in part by the cytokine, interleukin-21. This study
investigates the differentiation and regulation of Tfh cells,
major producers of IL-21, in the immune response to H. pylori
challenge. To better understand the conditions influencing the
promotion and inhibition of a chronically elevated Tfh
population, we used top-down and bottom-up approaches to
develop computational models of Tfh and T follicular regulatory
(Tfr) cell differentiation. Stability analysis was used to
characterize the presence of two bi-stable steady states in the
calibrated Tfh/Tfr models. Stochastic simulation was used to
illustrate the ability of the parameter set to dictate two
distinct behavioral patterns. Furthermore, sensitivity analysis
helped identify the importance of various parameters on the
establishment of Tfh and Tfr cell populations. The core network
model was expanded into a more comprehensive and predictive
model by including cytokine production and signaling pathways.
From the expanded network, the interaction between TGFB-Induced
Factor Homeobox 1 (Tgif1) and the retinoid X receptor (RXR) was
displayed to exert control over the determination of the Tfh
response. Model simulations predict that Tgif1 and RXR
respectively induce and curtail Tfh responses. This
computational hypothesis was validated experimentally by
assaying Tgif1, RXR and Tfh in stomachs of mice infected with
H. pylori.
The impulse of RXR as shown in the paper
(figure 7C) can be implemented by creating an event in the curated
SBML file.
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BIOMD0000000625.
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2024-09-02 | BIOMD0000000625 | BioModels
Project description:CD4 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.
2010-04-20 | GSE21380 | GEO
Project description:After activation, CD4+ helper T (Th) cells differentiate; into distinct effector subsets. Although chemokine; (C-X-C motif) receptor 5-expressing T follicular; helper (Tfh) cells are important in humoral immunity,; their developmental regulation is unclear. Here we; show that Tfh cells had a distinct gene expression; profile and developed in vivo independently of the; Th1 or Th2 cell lineages. Tfh cell generation was regulated; by ICOS ligand (ICOSL) expressed on B cells; and was dependent on interleukin-21 (IL-21), IL-6,; and signal transducer and activator of transcription; 3. However, unlike Th17 cells, differentiation of Tfh; cells did not require transforming growth factor; b (TGF-b) or Th17-specific orphan nuclear receptors; RORa and RORg in vivo. Finally, naive T cells activated; in vitro in the presence of IL-21 but not; TGF-b signaling preferentially acquired Tfh gene; expression and promoted germinal-center reactions; in vivo. This study thus demonstrates that Tfh is a; distinct Th cell lineage. Experiment Overall Design: Splenic CD4+CXCR5+ T cells were isolated from KLH-immunized mice and restimulated with anti-CD3 for 4 hours before total RNA preparation. Affymetrix gene chips were used to analyze their gene expression.
2008-10-21 | E-GEOD-11924 | biostudies-arrayexpress
Project description:Gene expression profiling was performed to access the changes in gene expression in melanomas from Pdk1-inactivated Brafv600E::Pten-/- mice. The expression profiles of the BrafV600E::Pten-/-::Pdk1-/- were compared to the BrafV600E::Pten-/-::Pdk+/+ genotypes. The analysis has identified several important signaling pathways in Pdk1-dependent melanomagenesis. Melanoma tumors from the BrafV600E::Pten-/-::Pdk1+/+ and BrafV600E::Pten-/-::Pdk1-/- genotypes were harvested and mRNA from each group was pooled to enable four biologically replicates analysis.
2013-09-17 | E-GEOD-42187 | biostudies-arrayexpress
Project description:CD4 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.
2010-04-20 | GSE21379 | GEO
Project description:Follicular helper CD4 T (Tfh) cells provide B cells with signals that are important for the generation of high-affinity Abs and immunological memory and, therefore, are critical for the protective immunity elicited by most human vaccines. In this study we sought to define the gene expression signature of bona fide GC Tfh and Tfh cells. The CD4+ T cell subsets CD45RO+CXCR5-, CD45RO+CXCR5int (Tfh cells), and CD45RO+CXCR5hi (GC Tfh cells) were isolated from 6 tonsil samples for gene expression analysis.
2013-11-12 | E-GEOD-50391 | biostudies-arrayexpress