title: Nrf2 activation by sulforaphane restores the age-related decrease of T(H)1 immunity: role of dendritic cells.
abstract: BACKGROUND
  The decrease in cellular immunity with aging is of considerable public health importance. Recent studies suggest that the redox 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.
  
  
  OBJECTIVE
  We sought (1) to elucidate the role of DC redox equilibrium in the decrease of contact hypersensitivity (CHS) and T(H)1 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 T(H)1 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.
  
  
  CONCLUSIONS
  SFN and NAC upregulate T(H)1 immunity in aging through a restoration of redox equilibrium.
authors.affiliation: Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Hyon-Jeen
authors.initials: HJ
authors.lastname: Kim
authors.forename: Berenice
authors.initials: B
authors.lastname: Barajas
authors.forename: Meiying
authors.initials: M
authors.lastname: Wang
authors.forename: Andre E
authors.initials: AE
authors.lastname: Nel
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D019264:Adoptive Transfer; D000375:Aging / Q000502:physiology*; D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017879:Isothiocyanates; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013454:Sulfoxides; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D013454:Sulfoxides; D013861:Thiocyanates; D015847:Interleukin-4; D007371:Interferon-gamma; C016766:sulforaphane; D005978:Glutathione; D000111:Acetylcysteine