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Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ.

Published version
Peer-reviewed

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Type

Article

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Authors

Innocentin, Silvia 
Matheson, Louise S 

Abstract

Ageing profoundly changes our immune system and is thought to be a driving factor in the morbidity and mortality associated with infectious disease in older people. We have previously shown that the impaired immunity to vaccination that occurs in aged individuals is partly attributed to the effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how age intrinsically affects Tfh cell formation in both mice and humans. We show increased formation of Tfh precursors (pre-Tfh) but no associated increase in germinal centre (GC)-Tfh cells in aged mice, suggesting age-driven promotion of only early Tfh cell differentiation. Mechanistically, we show that ageing alters TCR signalling which drives expression of the Notch-associated transcription factor, RBPJ. Genetic or chemical modulation of RBPJ or Notch rescues this age-associated early Tfh cell differentiation, and increased intrinsic Notch activity recapitulates this phenomenon in younger mice. Our data offer mechanistic insight into the age-induced changes in T-cell activation that affects the differentiation and ultimately the function of effector T cells.

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Keywords

CXCR5, Notch, RBPJ, T follicular helper cells, age, Aging, Animals, Cell Differentiation, Female, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Mice, Receptors, CXCR5, T Follicular Helper Cells

Journal Title

Aging Cell

Conference Name

Journal ISSN

1474-9718
1474-9726

Volume Title

20

Publisher

Wiley