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Age promotes abortive T follicular helper cell differentiation by increasing Notch signalling.

ABSTRACT: Age promotes abortive T follicular helper cell differentiation by increasing Notch signalling.

PROVIDER: PRJNA627949 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11607045.fastq.gz	Fastqsanger.gz
	SRR11607046.fastq.gz	Fastqsanger.gz
	SRR11607047.fastq.gz	Fastqsanger.gz
	SRR11607048.fastq.gz	Fastqsanger.gz
	SRR11607049.fastq.gz	Fastqsanger.gz

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Age promotes abortive T follicular helper cell differentiation by increasing Notch signalling.

Project description:Ageing profoundly changes our immune system. It is thought to be a driving factor in the morbidity and mortality associated with infectious disease in the elderly. T follicular helper (Tfh) cells are essential for the generation of long-lasting protective immunity yet we do not know how ageing effect the ability to generate these cells. In this study we examined the effect of age on Tfh-precursor formation in both humans. We found that age drives increased formation of these cells. Further investigation showed that T cells from older donors had altered T cell receptor signalling, increased expression of CXCR5. RNA-Sequencing analysis of cells during differentiation highlighted the Notch-associated transcription factor, RBPJ, as important. Importantly, genetic or chemical modulation of the Notch pathway was able to rescue the age-associated increase in CXCR5 expression and aberrant accumulation of Tfh-precursors. Despite accumulation of Tfh-precursors, increased Notch activation was not sufficient for further differentiation into full Germinal Center (GC)-Tfh cells. This cell-intrinsic failure to make GC-Tfh cells likely contributes to the defective GC responses in ageing.

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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.

2009-08-07 | E-GEOD-16697 | biostudies-arrayexpress

Murine follicular helper T cells

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

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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Genome-wide Ezh2 and Tcf1 occupance in follicular helper T cells

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The BNT162b2 vaccine elicits robust lymph node T follicular helper cell responses

Project description:COVID-19 mRNA vaccines generate high concentrations of circulating anti-Spike antibodies and Spike-specific CD4+ T cells following prime-boost vaccination. It is not yet clear if vaccine-induced CD4+ T cell responses in the draining lymph node contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we found large populations of Spike-specific CD4+ T follicular helper cells in the draining lymph node. A broadly immunodominant HLA-DPB1*04-restricted response to Spike166-180 composes one of the largest populations of T follicular helper cells in individuals with this allele, which is itself among the most common HLA alleles in the human population. Spike-specific T follicular helper cells are present in the lymph node 30 days after vaccine boost and persist in some individuals more than 170 days. Collectively, our results underscore the key role that robust T follicular helper cell responses play in the establishment of long-term immunity in this very efficacious human vaccine.

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