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Nrf2 activation by sulforaphane restores the age-related decrease of Th1 immunity: Role of dendritic cells – Source: Journal of Allergy and Clinical Immunology, Mar 6, 2008

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By Hyon-Jeen Kim, PhD, Andre E. Nel, MD, PhD, et al. • • March 10, 2008

[Note: Nrf2 is a protein which serves as a “master regulator” of the body's overall antioxidant response and is capable of switching on hundreds of antioxidant and rejuvenating genes and enzymes. Th1 cells are “hormonal messengers responsible for most biological effects in the immune system.” Dendritic cells pick up antigens from the skin or mucous membranes & present them to the T cells.]

Background: The decrease in cellular immunity with aging is of considerable public health importance. Recent studies suggest that the redox [reduction/oxidation] equilibrium of dendritic cells (DCs) is a key factor in maintaining protective cellular immunity and that a disturbance of this homeostatic mechanism could contribute to immune senescence [aging].

Objectives: We sought:

1. To elucidate the role of DC redox equilibrium in the decrease of contact hypersensitivity (CHS) and Th1 immunity during aging, and

2. To determine how restoration of glutathione (GSH) levels by the Nrf2-mediated antioxidant defense pathway affects this decrease.

Methods: We assessed the effect of Nrf2 deficiency and boosting of GSH levels by the Nrf2 agonist sulforaphane 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 DCs ex vivo before adoptive transfer and in vivo challenge.

Results: Aging was associated with a decreased CHS response that was accentuated by Nrf2 deficiency. Systemic SFN treatment reversed this decrease through Nrf2-mediated antioxidant enzyme expression and GSH synthesis. Adoptive transfer of DCs from old animals induced a weakened CHS response in recipient animals. Treatment of DCs from old animals with SFN or NAC ex vivo restored the in vivo challenge response.

Conclusion: SFN and NAC upregulate Th1 immunity in aging through a restoration of redox equilibrium. [For a plain-language interpretation of the study findings, see “UCLA study finds that broccoli may help boost the aging immune system.”]

Source: Journal of Allergy and Clinical Immunology, Mar 6, 2008. [E-pub ahead of print] PMID: 18325578, by kim HJ, Barajas B, Wang M, Nel AE. Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA 90095 [E-mail:]

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