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Upregulation of TFH profile in absence of Ets1 expression

ABSTRACT: To characterize the effect of loss of Ets1 in Non-TFH and TFH cells, we performed gene expression RNAseq analysis for T follicular helper (TFH) and Non-T follicular helper (Non-TFH) cells in WT (Ets1 fl/fl) and Ets1 KO (CD4-cre Ets1 fl/fl) mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE110595 | GEO | 2019/03/03

REPOSITORIES: GEO

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Expression Data from in vivo Tfh vs GC Tfh vs non-Tfh

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.

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Project description:Upregulation of TFH profile in absence of Ets1 expression

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Ets1 modulates epigentic landscape of key TFH genes in T naïve cells

Project description:Ets1 can directly bind key TFH genes, regulating their expression . Loss of Ets1 results in the pre-mature expression of TFH-genes in Non-TFH cells. We wished to analyze if loss of Ets1 correlated with changes in chromatin accessibility especially in TFH gene loci.

2019-03-03 | GSE110594 | GEO

Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH)

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Transcriptional analysis of human tonsil Tfh cells

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