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Role of nsd2 in Follicular helper T cells

ABSTRACT: Role of nsd2 in Follicular helper T cells

PROVIDER: PRJNA540602 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8994385.fastq.gz	Fastqsanger.gz
	SRR8994386.fastq.gz	Fastqsanger.gz
	SRR8994387.fastq.gz	Fastqsanger.gz
	SRR8994388.fastq.gz	Fastqsanger.gz

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Role of nsd2 in Follicular helper T cells

Project description:Follicular helper T cell (Tfh) provide essential help for humoral immune response. However, how Tfh differentiation is epigenetically regulated remains incompletely understood. Here we found that H3K36me2 methyltransferase Nsd2 is required for Tfh differentiation. Lack of Nsd2 leads to reduced Tfh generation and germinal center response. Mice with Nsd2 deficiency in T cells have reduced capability of chronic virus control. To understand the molecular mechanism by which Nsd2 regulates Tfh differentiation, RNA-seq analysis of Nsd2 wildtype and knockout Tfh cells were performed.

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Murine follicular helper T cells

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Transcription profiling of mouse vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH)

Project description:Analysis 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). Experiment Overall Design: Analysis 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.

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

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Project description:IL-2 production defines precursors fated to become T Follicular Helper cells

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

Project description:IL-2 production defines precursors fated to become T Follicular Helper cells

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Transcription profiling of WT and NFAT2 KO follicular helper CD4 T cells and non follicular helper CD4 T cell populations

Project description:Comparatative gene expression analysis for wild type and NFAT2-/- CD4 T cell subsets including follicular helper CD4+ T (TFH) cells, activated CD4+ T cells, and naive CD4+ T cells isolated from the spleen.

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

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Follicular Regulatory T Cells Regulate the Development of Cytotoxic-like Follicular Helper T Cells

Project description:T follicular regulatory (TFR) cells are found in the germinal center (GC) response and help shape the antibody (Ab) response. Whether TFR cells have a suppressive role, a helper role or both types of roles in the GC is unclear. Here, we addressed TFR cell function using 3 different strains of TFR cell mutant mice. After immunization, GC B cells but not T follicular helper (TFH) cell positively correlated with TFR cell levels. Using a gene profiling approach, we found that TFH cells from TFR-deficient mice showed strong up-regulation of granzyme B (Gzmb) and other effector CD8 T cell genes, many of which were Stat4 dependent. This aberrant cytotoxic T cell gene profile was increased in TFR-deficient mice crossed on a pro-inflammatory background. We detected Gzmb+ and Eomesodermin+ TFH cells and a higher rate of apoptotic GC B cells in the absence of TFR cells. Klrg1+ TFH cells expressed higher Gzmb and less IL-4 and IL-21. Our data show that TFR cells repress the development of abnormal cytotoxic TFH cells that correlate with a lower GC and Ab response. This data shows a novel mode of helper function for TFR cells in the GC response.

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