The Journal of Allergy and Clinical Immunology
Volume 121, Issue 5 , Pages 1255-1261.e7 , May 2008

Nrf2 activation by sulforaphane restores the age-related decrease of TH1 immunity: Role of dendritic cells

Received 14 September 2007 ,Revised 30 November 2007 ,Accepted 11 January 2008.

References 

  1. Fulop T, Larbi A, Dupuis G, Pawelec G. Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction pathways with ageing—a biochemical paradigm for the ageing immune system. Arthritis Res Ther. 2003;5:290–302
  2. Harman D. Ageing: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11:298–300
  3. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997;236:313–322
  4. Xiao GG, Wang M, Li N, Loo JA, Nel AE. Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line. J Biol Chem. 2003;278:50781–50790
  5. Suh JH, Shenvi SV, Dixon BM, Liu H, Jaiswal AK, Liu RM, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004;101:3381–3386
  6. Shih PH, Yen GC. Differential expressions of antioxidant status in aging rats: the role of transcriptional factor Nrf2 and MAPK signaling pathway. Biogerontology. 2007;8:71–80
  7. Hirayama A, Yoh K, Nagase S, Ueda A, Itoh K, Morito N, et al. EPR imaging of reducing activity in Nrf2 transcriptional factor-deficient mice. Free Radic Biol Med. 2003;34:1236–1242
  8. Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, Yamamoto M, Biswal S. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res. 2002;62:5196–5203
  9. Kim HJ, Nel AE. The role of phase II antioxidant enzymes in protecting memory T cells from spontaneous apoptosis in young and old mice. J Immunol. 2005;175:2948–2959
  10. Thimmulappa RK, Lee H, Rangasamy T, Reddy SP, Yamamoto M, Kensler TW, et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J Clin Invest. 2006;116:984–995
  11. Chan RC, Wang M, Li N, Yanagawa Y, Onoe K, Lee JJ, et al. Pro-oxidative diesel exhaust particle chemicals inhibit lipopolysaccharide-induced dendritic cell responses involved in T-helper differentiation. J Allergy Clin Immunol. 2006;118:455–465
  12. Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Natl Acad Sci U S A. 1998;95:3071–3076
  13. Kim HJ, Barajas B, Chan RC, Nel AE. Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: implications for systemic disease and immunosenescence. J Allergy Clin Immunol. 2007;119:1225–1233
  14. Chan K, Kan YW. Nrf2 is essential for protection against acute pulmonary injury in mice. Proc Natl Acad Sci U S A. 1997;96:12731–12736
  15. Gaspari AA, Katz SI. Contact hypersensitivity. In:  Coligan JE,  Kruisbeek AM,  Margulies DH,  Shevach EM,  Strober W editor. Current protocols in immunology. Hoboken (NJ): John Wiley & Sons; 2003;
  16. Agnello D, Lankford CS, Bream J, Morinobu A, Gadina M, O'Shea JJ, et al. Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights. J Clin Immunol. 2003;23:147–161
  17. Li J, Stein TD, Johnson JA. Genetic dissection of systemic autoimmune disease in Nrf2-deficient mice. Physiol Genomics. 2004;18:261–272
  18. Kantengwa S, Jornot L, Devenoges C, Nicod LP. Superoxide anions induce the maturation of human dendritic cells. Am J Respir Crit Care Med. 2003;167:431–437
  19. Lane N. A unifying view of ageing and disease: the double-agent theory. J Theor Biol. 2003;225:531–540
  20. D'Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma- production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med. 1993;178:1041–1048
  21. Wallet MA, Sen P, Tisch R. Immunoregulation of dendritic cells. Clin Med Res. 2005;3:166–175
  22. Rivollier A, Perrin-Cocon L, Luche S, Diemer H, Strub JM, Hanau D, et al. High expression of antioxidant proteins in dendritic cells: possible implications in atherosclerosis. Mol Cell Proteomics. 2006;5:726–736
  23. Thoren FB, Betten A, Romero AI, Hellstrand K. Cutting edge: antioxidative properties of myeloid dendritic cells: protection of T cells and NK cells from oxygen radical-induced inactivation and apoptosis. J Immunol. 2007;179:21–25
  24. Lung TL, Saurwein-Teissl M, Parson W, Schonitzer D, Grubeck-Loebenstein B. Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. Vaccine. 2000;18:1606–1612
  25. Miller C, Kelsoe G, Han S. Lack of B7-2 expression in the germinal centers of aged mice. Aging Immunol Infect Dis. 1994;5:249–257
  26. Pawelec G, Solana R, Remarque E, Mariani E. Impact of aging on innate immunity. J Leukoc Biol. 1998;64:703–712
  27. Shurin MR, Shurin GV, Chatta GS. Aging and the dendritic cell system: implication for cancer. Crit Rev Oncol Hematol. 2007;64:90–105
  28. Meydani M, Lipman RD, Han SN, Wu D, Beharka A, Martin KR, et al. The effect of long-term dietary supplementation with antioxidants. Ann N Y Acad Sci. 1998;854:352–360
  29. Särnstrand B, Jansson AH, Matuseviciene G, Scheynius A, Pierrou S, Bergstrand H. N,N′-Diacetyl-L-cystine-the disulfide dimer of N-acetylcysteine-is a potent modulator of contact sensitivity/delayed type hypersensitivity reactions in rodents. J Pharmacol Exp Ther. 1999;288:1174–1184
  30. Bruchhausen S, Zahn S, Valk E, Knop J, Becker D. Thiol antioxidants block the activation of antigen-presenting cells by contact sensitizers. J Invest Dermatol. 2003;121:1039–1044
  31. Becker D, Valk E, Zahn S, Brand P, Knop J. Coupling of contact sensitizers to thiol groups is a key event for the activation of monocytes and monocyte-derived dendritic cells. J Invest Dermatol. 2003;120:233–238

 Supported by US Public Health Science support from the National Institute of Ageing (RO1 AG14992), the UCLA Claude D. Pepper Older Americans Independence Center (5P30 AG028748), and the National Institute of Allergy and Infectious Diseases–funded UCLA Asthma and Allergic Disease Clinical Research Center (U19 AI070453).

 Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

PII: S0091-6749(08)00148-6

doi: 10.1016/j.jaci.2008.01.016

The Journal of Allergy and Clinical Immunology
Volume 121, Issue 5 , Pages 1255-1261.e7 , May 2008

Article Tools

* Image Usage & Resolution