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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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