Age promotes abortive T follicular helper cell differentiation by increasing Notch signalling.
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ABSTRACT: 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.
ORGANISM(S): Homo sapiens
PROVIDER: GSE149319 | GEO | 2021/11/01
REPOSITORIES: GEO
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