The decline in cellular immunity with ageing is of considerable public health importance. Recent studies suggest that the redox equilibrium of dendritic cells (DC) is a key factor in maintaining protective cellular immunity and that a disturbance of this homeostatic mechanism could contribute to immune senescence.
(i) To elucidate the role of DC redox equilibrium in the decline of contact hypersensitivity (CHS) and Th1 immunity during ageing; (ii) To determine how restoration of glutathione (GSH) levels by the Nrf2-mediated antioxidant defense pathway impacts this decline.
We assessed the effect of Nrf2 deficiency and boosting of GSH levels by the Nrf2 agonist, sulforaphane (SFN), or the thiol precursor, N-acetyl cysteine (NAC), on the CHS response to contact antigens in old mice. We studied the effect of SFN and NAC on restoring Th1 immunity by treating DC ex vivo before adoptive transfer and in vivo challenge.
Ageing was associated with a decreased CHS response that was accentuated by Nrf2 deficiency. Systemic SFN treatment reversed this decline through Nrf2-mediated antioxidant enzyme expression and GSH synthesis. Adoptive transfer of DC from old animals induced a weakened CHS response in recipient animals. Treatment of DC from old animals with SFN or NAC ex vivo restored the in vivo challenge response.
SFN and NAC up-regulate Th1 immunity in ageing through a restoration of redox equilibrium.
Restoration of the redox equilibrium in the immune system could restore or delay the decline of cellular immunity with ageing.