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

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 o...

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Bibliographic Details
Published in:Aging cell 2021-01, Vol.20 (1), p.e13295-n/a
Main Authors: Webb, Louise M. C., Fra‐Bido, Sigrid, Innocentin, Silvia, Matheson, Louise S., Attaf, Noudjoud, Bignon, Alexandre, Novarino, Julien, Fazilleau, Nicolas, Linterman, Michelle A.
Format: Article
Language:English
Subjects:
Age
Aging
Antigens
B cells
Cell activation
Cell differentiation
Collaboration
CXCR5
Disease susceptibility
Effector cells
Geriatry and gerontology
Health aspects
Human health and pathology
Immune system
Infections
Infectious diseases
Influenza
Life Sciences
Lymphatic system
Lymphocytes
Lymphocytes T
Morbidity
Notch
Older people
Original
RBPJ
T cell receptors
T cells
T follicular helper cells
Vaccination
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Summary: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. Ageing alters TCR signalling which drives expression of the Notch‐associated transcription factor, RBPJ. This results in enhanced differentiation into T follicular helper cell precursors.
ISSN:1474-9718
1474-9726
1474-9728
DOI:10.1111/acel.13295