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STAT4 and T-bet control follicular helper T cells development in viral infections

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE105808 | GEO | 2017/11/21

SECONDARY ACCESSION(S): PRJNA415458

REPOSITORIES: GEO

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STAT4 and T-bet control follicular helper T cell development in viral infections.

Project description: Not available

| S-EPMC5748849 | biostudies-literature

STAT4 and T-bet control follicular helper T cells development in viral infections [ATAC-seq]

Project description:Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and proliferation, and guide their differentiation and Ig isotype switching by delivering contact-dependent and soluble factors, including IL-21, IL-4, IL-9, and IFN-g. IL-21 and IFN-g are co-expressed by Tfh cells during acute and chronic infections, but transcriptional regulation of these cytokines in the GC is incompletely understood. We show that the Th1 transcriptional regulators T-bet and STAT4 are co-expressed with Bcl6 in Tfh cells following acute murine lymphocytic choriomeningitis virus infection, albeit with temporal decline in T-bet expression as the GC response evolved. T-bet was important for Tfh cell production of IFN-g, but not IL-21, and for the generation of a robust germinal center reaction. STAT4, phosphorylated in Tfh cells upon infection, was required for their expression of T-bet and Bcl6, and that of IFN-g and IL-21. These data indicate that T-bet is concomitantly expressed with Bcl6 in Tfh cells and is required alongside STAT4 phosphorylation to coordinate Tfh cell IL-21 and IFN-g production, and for promotion of the GC response following acute viral challenge.

2017-11-22 | GSE105807 | GEO

STAT4 and T-bet control follicular helper T cells development in viral infections [RNA-seq]

2017-11-22 | GSE105806 | GEO

STAT4 and T-bet control follicular helper T cells development in viral infections

Project description:STAT4 and T-bet control follicular helper T cells development in viral infections

| PRJNA415458 | ENA

STAT4 and T-bet control follicular helper T cells development in viral infections [RNA-seq]

Project description:STAT4 and T-bet control follicular helper T cells development in viral infections [RNA-seq]

| PRJNA415460 | ENA

STAT4 and T-bet control follicular helper T cells development in viral infections [ATAC-seq]

Project description:STAT4 and T-bet control follicular helper T cells development in viral infections [ATAC-seq]

| PRJNA415459 | ENA

Transcription factor Achaete-Scute homologue 2 initiates T follicular helper cell development

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-01 | E-GEOD-52840 | biostudies-arrayexpress

Differential Expression of IL-2 Defines CD4 T cells fated for Follicular Helper and Non-follicular Helper Development

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-09-19 | GSE116608 | GEO

Early T-helper 1 Differentiation Is Marked by A Follicular Helper-like Transition: Differential Roles of STAT4 and T-bet

Project description:Follicular helper T (Tfh) cells comprise an important subset of helper T cells; however, their relationship with other helper lineages is incompletely understood. Herein, we show IL-12 acting via signal transducer and activator of transcription 4 (STAT4) induced both Il21 and Bcl6 genes, generating cells with features of both Tfh and Th1 cells. However, STAT4 also induced T-bet. Using ChIP-seq, we defined the genome-wide targets of T-bet and found that it repressed Bcl6 and other markers of Tfh cells, thereby attenuating the nascent Tfh-like phenotype in the late phase of Th1 specification. Finally, Tfh-like T cells were rapidly generated following Toxoplasma gondii infection in mice, but T-bet constrained Tfh cells expansion and consequent germinal center formation and antibody production. Our data argue that Tfh and Th1 share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh functionalities, promoting full Th1 differentiation. The roles of STAT4 and T-bet to determine T helper cell fate were investigated by comparing DNA binding profiles of STAT4 and T-bet in Th1 conditions. The functional outcome was further evaluated by profiling DNase hypersensitivity sites and histone epigenetic marks between WT and STAT4-deficient or T-bet-deficient T cells in Th1 conditions.

2011-12-27 | E-GEOD-33802 | biostudies-arrayexpress

Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection.

Project description: Not available

| S-EPMC6711398 | biostudies-literature