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