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Effects of Aryl-Hydrocarbon Ligands on Dendritic Cell Maturation

Received: 24 July 2013     Published: 10 September 2013
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Abstract

Aryl-hydrocarbon receptor (AhR) is a cytosolic receptor found in many cells, including immune cells, and its function has been implicated in metabolic and transcriptional control of immune regulation. In the present study we have investigated the effect of the AhR-ligands, FICZ, I3C, curcumin, quercetin and the ligands precursor tryptophan, on bone marrow-derived dendritic cell (BMDC) maturation and immuno-stimulatory or immuno-suppressive phenotypes. We find that immature and mature BMDC express intracellular AhR. Treatment of BMDC with AhR-ligands during LPS-induced BMDC maturation had no significant effect on the expression of MHC class II, CD40 and CD86, with the exception of I3C which suppressed CD40 expression by BMDC at high doses. However, all AhR-ligands significantly enhanced the secretion of pro-inflammatory cytokines, including IL-6, IL-12p40, TNF-α, and IL-1β. In contrast, only the AhR-ligands FICZ and I3C increased IL-10 and TGF-β secretion. Tryptophan, curcumin, and quercetin significantly suppressed IL-10 secretion without affecting TGF-β secretion. Finally, FICZ and I3C significantly enhanced the expression of the tolerogenic DC enzyme, indoleamine-2, 3-dioxygenase (IDO), while tryptophan, curcumin and quercetin did not change IDO expression. These results suggest that FICZ and I3C can promote a tolerogenic BMDC phenotype consistent with suppression of immune responses by enhancing the secretion of anti-inflammatory cytokines and increasing IDO expression. In contrast, tryptophan, curcumin and quercetin can promote an immuno-stimulatory BMDC phenotype, secreting elevated pro-inflammatory cytokines, which could help in skewing T cell responses towards the development of effector CD4 and CD8 T cell subsets.

Published in International Journal of Immunology (Volume 1, Issue 3)
DOI 10.11648/j.iji.20130103.11
Page(s) 24-34
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2013. Published by Science Publishing Group

Keywords

Curcumin, Tryptophan, Quercetin, FICZ, I3C, TGF-β, IL-10, IDO

References
[1] Esser, C., A. Rannug, and B. Stockinger, The aryl hydrocarbon receptor in immunity. Trends Immunol, 2009. 30(9): p. 447-54.
[2] Cua, D.J. and C.M. Tato, Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol, 2010. 10(7): p. 479-89.
[3] Komura, K., et al., Aryl hydrocarbon receptor/dioxin receptor in human monocytes and macrophages. Mol Cell Biochem, 2001. 226(1-2): p. 107-18.
[4] Frericks, M., et al., Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice. Biol Chem, 2006. 387(9): p. 1219-26.
[5] Denison, M.S. and S.R. Nagy, Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol, 2003. 43: p. 309-34.
[6] Schecter, A., et al., Dioxins: an overview. Environ Res, 2006. 101(3): p. 419-28.
[7] Walker, L.S. and A.K. Abbas, The enemy within: keeping self-reactive T cells at bay in the periphery. Nat Rev Immunol, 2002. 2(1): p. 11-9.
[8] Sakaguchi, S., et al., Regulatory T cells and immune tolerance. Cell, 2008. 133(5): p. 775-87.
[9] Wan, Y.Y. and R.A. Flavell, How diverse--CD4 effector T cells and their functions. J Mol Cell Biol, 2009. 1(1): p. 20-36.
[10] Murphy, K.M. and B. Stockinger, Effector T cell plasticity: flexibility in the face of changing circumstances. Nat Immunol, 2010. 11(8): p. 674-80.
[11] Vlad, G., R. Cortesini, and N. Suciu-Foca, License to heal: bidirectional interaction of antigen-specific regulatory T cells and tolerogenic APC. J Immunol, 2005. 174(10): p. 5907-14.
[12] Coombes, J.L. and F. Powrie, Dendritic cells in intestinal immune regulation. Nat Rev Immunol, 2008. 8(6): p. 435-46.
[13] Mellor, A.L. and D.H. Munn, IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol, 2004. 4(10): p. 762-74.
[14] Mezrich, J.D., et al., An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol, 2010. 185(6): p. 3190-8.
[15] Nguyen, N.T., et al., Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc Natl Acad Sci U S A, 2010. 107(46): p. 19961-6.
[16] Vogel, C.F., et al., Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2, 3-dioxygenase. Biochem Biophys Res Commun, 2008. 375(3): p. 331-5.
[17] Bankoti, J., et al., Functional and phenotypic effects of AhR activation in inflammatory dendritic cells. Toxicol Appl Pharmacol, 2010. 246(1-2): p. 18-28.
[18] Simones, T. and D.M. Shepherd, Consequences of AhR activation in steady-state dendritic cells. Toxicol Sci, 2011. 119(2): p. 293-307.
[19] Apetoh, L., et al., The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat Immunol, 2010. 11(9): p. 854-61.
[20] Gandhi, R., et al., Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3 (+) regulatory T cells. Nat Immunol, 2010. 11(9): p. 846-53.
[21] Bankoti, J., et al., Effects of TCDD on the fate of naive dendritic cells. Toxicol Sci, 2010. 115(2): p. 422-34.
[22] Veldhoen, M., et al., The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature, 2008. 453(7191): p. 106-9.
[23] Quintana, F.J., et al., Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature, 2008. 453(7191): p. 65-71.
[24] Veldhoen, M., et al., Natural agonists for aryl hydrocarbon receptor in culture medium is essential for optimal differentiation of Th17 T cells. J Exp Med, 2009. 206(1): p. 43-9.
[25] Lutz, M.B., et al., An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods, 1999. 223(1): p. 77-92.
[26] Ciolino, H.P., et al., Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells. Biochem Pharmacol, 1998. 56(2): p. 197-206.
[27] Ciolino, H.P., P.J. Daschner, and G.C. Yeh, Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Biochem J, 1999. 340 ( Pt 3): p. 715-22.
[28] Bjeldanes, L.F., et al., Aromatic hydrocarbon responsiveness -receptor agonists generated from indole - 3-carbinol in vitro and in vivo: comparisons with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Proc Natl Acad Sci U S A, 1991. 88(21): p. 9543-7.
[29] Kerkvliet, N.I., Recent advances in understanding the mechanisms of TCDD immunotoxicity. Int Immunopharmacol, 2002. 2(2-3): p. 277-91.
[30] Hilkens, C.M., J.D. Isaacs, and A.W. Thomson, Development of dendritic cell-based immunotherapy for autoimmunity. Int Rev Immunol, 2010. 29(2): p. 156-83.
[31] Bright, J.J., Curcumin and autoimmune disease. Adv Exp Med Biol, 2007. 595: p. 425-51.
[32] Cong, Y., et al., Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine-protective regulatory T cells. Eur J Immunol, 2009. 39(11): p. 3134-46.
[33] Kim, G.Y., et al., Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-kappa B as potential targets. J Immunol, 2005. 174(12): p. 8116-24.
[34] Jeong, Y.I., et al., Curcumin suppresses the induction of indoleamine 2,3-dioxygenase by blocking the Janus-activated kinase-protein kinase Cdelta-STAT1 signaling pathway in interferon- gamma- stimulated murine dendritic cells. J Biol Chem, 2009. 284(6): p. 3700-8.
[35] Jung, I.D., et al., COX-2 and PGE2 signaling is essential for the regulation of IDO expression by curcumin in murine bone marrow-derived dendritic cells. Int Immunopharmacol, 2010. 10(7): p. 760-8.
[36] Huang, R.Y., et al., Immunosuppressive effect of quercetin on dendritic cell activation and function. J Immunol, 2011. 184(12): p. 6815-21.
[37] Miller, J.I., Modulation of Dendritic Cells and Autoimmunity by Apoptotic and Necrotic Cells, in Disease Department. 2011, The University of Manchester: London. p. 187.
[38] de Waard, W.J., et al., Gene expression profiling in Caco-2 human colon cells exposed to TCDD, benzo [a] pyrene, and natural Ah receptor agonists from cruciferous vegetables and citrus fruits. Toxicol In Vitro, 2008. 22(2): p. 396-410.
[39] Rinaldi, A.L., et al., Curcumin activates the aryl hydrocarbon receptor yet significantly inhibits (-) benzo (a) pyrene- 7R-trans- 7, 8-dihydrodiol bioactivation in oral squamous cell carcinoma cells and oral mucosa. Cancer Res, 2002. 62(19): p. 5451-6.
[40] Ashida, H., et al., Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin. FEBS Lett, 2000. 476(3): p. 213-7.
[41] Zal, T., et al., Mechanisms of tolerance induction in major histocompatibility complex class II-restricted T cells Specific for a blood-borne self-antigen. J Exp Med, 1994. 180 (8): p. 2089-99.
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    Hana’a A. Abu-Rezq, Douglas G. Millar. (2013). Effects of Aryl-Hydrocarbon Ligands on Dendritic Cell Maturation. International Journal of Immunology, 1(3), 24-34. https://doi.org/10.11648/j.iji.20130103.11

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    Hana’a A. Abu-Rezq; Douglas G. Millar. Effects of Aryl-Hydrocarbon Ligands on Dendritic Cell Maturation. Int. J. Immunol. 2013, 1(3), 24-34. doi: 10.11648/j.iji.20130103.11

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    AMA Style

    Hana’a A. Abu-Rezq, Douglas G. Millar. Effects of Aryl-Hydrocarbon Ligands on Dendritic Cell Maturation. Int J Immunol. 2013;1(3):24-34. doi: 10.11648/j.iji.20130103.11

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  • @article{10.11648/j.iji.20130103.11,
      author = {Hana’a A. Abu-Rezq and Douglas G. Millar},
      title = {Effects of Aryl-Hydrocarbon Ligands on Dendritic Cell Maturation},
      journal = {International Journal of Immunology},
      volume = {1},
      number = {3},
      pages = {24-34},
      doi = {10.11648/j.iji.20130103.11},
      url = {https://doi.org/10.11648/j.iji.20130103.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20130103.11},
      abstract = {Aryl-hydrocarbon receptor (AhR) is a cytosolic receptor found in many cells, including immune cells, and its function has been implicated in metabolic and transcriptional control of immune regulation. In the present study we have investigated the effect of the AhR-ligands, FICZ, I3C, curcumin, quercetin and the ligands precursor tryptophan, on bone marrow-derived dendritic cell (BMDC) maturation and immuno-stimulatory or immuno-suppressive phenotypes. We find that immature and mature BMDC express intracellular AhR. Treatment of BMDC with AhR-ligands during LPS-induced BMDC maturation had no significant effect on the expression of MHC class II, CD40 and CD86, with the exception of I3C which suppressed CD40 expression by BMDC at high doses. However, all AhR-ligands significantly enhanced the secretion of pro-inflammatory cytokines, including IL-6, IL-12p40, TNF-α, and IL-1β. In contrast, only the AhR-ligands FICZ and I3C increased IL-10 and TGF-β secretion. Tryptophan, curcumin, and quercetin significantly suppressed IL-10 secretion without affecting TGF-β secretion. Finally, FICZ and I3C significantly enhanced the expression of the tolerogenic DC enzyme, indoleamine-2, 3-dioxygenase (IDO), while tryptophan, curcumin and quercetin did not change IDO expression. These results suggest that FICZ and I3C can promote a tolerogenic BMDC phenotype consistent with suppression of immune responses by enhancing the secretion of anti-inflammatory cytokines and increasing IDO expression. In contrast, tryptophan, curcumin and quercetin can promote an immuno-stimulatory BMDC phenotype, secreting elevated pro-inflammatory cytokines, which could help in skewing T cell responses towards the development of effector CD4 and CD8 T cell subsets.},
     year = {2013}
    }
    

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  • TY  - JOUR
    T1  - Effects of Aryl-Hydrocarbon Ligands on Dendritic Cell Maturation
    AU  - Hana’a A. Abu-Rezq
    AU  - Douglas G. Millar
    Y1  - 2013/09/10
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    DO  - 10.11648/j.iji.20130103.11
    T2  - International Journal of Immunology
    JF  - International Journal of Immunology
    JO  - International Journal of Immunology
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    SN  - 2329-1753
    UR  - https://doi.org/10.11648/j.iji.20130103.11
    AB  - Aryl-hydrocarbon receptor (AhR) is a cytosolic receptor found in many cells, including immune cells, and its function has been implicated in metabolic and transcriptional control of immune regulation. In the present study we have investigated the effect of the AhR-ligands, FICZ, I3C, curcumin, quercetin and the ligands precursor tryptophan, on bone marrow-derived dendritic cell (BMDC) maturation and immuno-stimulatory or immuno-suppressive phenotypes. We find that immature and mature BMDC express intracellular AhR. Treatment of BMDC with AhR-ligands during LPS-induced BMDC maturation had no significant effect on the expression of MHC class II, CD40 and CD86, with the exception of I3C which suppressed CD40 expression by BMDC at high doses. However, all AhR-ligands significantly enhanced the secretion of pro-inflammatory cytokines, including IL-6, IL-12p40, TNF-α, and IL-1β. In contrast, only the AhR-ligands FICZ and I3C increased IL-10 and TGF-β secretion. Tryptophan, curcumin, and quercetin significantly suppressed IL-10 secretion without affecting TGF-β secretion. Finally, FICZ and I3C significantly enhanced the expression of the tolerogenic DC enzyme, indoleamine-2, 3-dioxygenase (IDO), while tryptophan, curcumin and quercetin did not change IDO expression. These results suggest that FICZ and I3C can promote a tolerogenic BMDC phenotype consistent with suppression of immune responses by enhancing the secretion of anti-inflammatory cytokines and increasing IDO expression. In contrast, tryptophan, curcumin and quercetin can promote an immuno-stimulatory BMDC phenotype, secreting elevated pro-inflammatory cytokines, which could help in skewing T cell responses towards the development of effector CD4 and CD8 T cell subsets.
    VL  - 1
    IS  - 3
    ER  - 

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Author Information
  • Aridland Agricultural Production Program, Environment and Life Sciences Centre, Kuwait Institute for Scientific Research, Shuwaikh, Kuwait

  • The University of Manchester, Faculty of Life Sciences, Immunology Group, Manchester, United Kingdom

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