Advertisement

Aryl Hydrocarbon Receptor: An Environmental Sensor in Control of Allergy Outcomes

  • Marco Gargaro
  • Matteo Pirro
  • Giorgia Manni
  • Antonella De Luca
  • Teresa Zelante
  • Francesca FallarinoEmail author
Chapter
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)

Abstract

The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AhR) has immune-modulating functions and responds to a wide variety of small molecules. Since AhR is highly expressed in cells at body surfaces, such as skin, gut mucosa and particularly in mucosal-associated lymphocytes, this molecule is perfectly positioned to be a sensor of external environmental signals. The role of AhR in the balance of immunity and tolerance and in the control of local homeostasis has been clearly demonstrated in recent years [Kiss et al., Science (New York, NY) 334(6062):1561–1565, 2011; Li et al., Cell 147(3):629–640, 2011]. Deletion of AhR in mice resulted in altered composition of gut microbiota, impaired function and inflammatory immune activation of gut epithelium. In addition to xenobiotics, AhR ligands now include endogenous metabolites, dietary derivatives and bacterial metabolites (Denison and Nagy. Annu Rev Pharmacol Toxicol 43:309–334, 2003). Xenobiotics such as dietary components, products of microbiota, and ubiquitous environmental pollutants may have shaped the AhR system in intestinal epithelia or other body surfaces during millions of years of evolution. Thus, the crosstalk among the dietary components/xenobiotics, AhR and the gut microbiome appears to be an important factor in the maintenance of the mucosal immunity and immune homeostasis. These exciting discoveries provide a novel perspective for the biological role of AhR, which has been originally studied only as a sensor of toxicants, but which has been now implicated in a wide range of human conditions, including autoimmune and allergic disorders.

Keywords

Aryl hydrocarbon receptor Environmental sensor Tissue barrier Indoles Immune regulation 

References

  1. Ashida H, Nishiumi S, Fukuda I (2008) An update on the dietary ligands of the AhR. Expert Opin Drug Metab Toxicol 4(11):1429–1447.  https://doi.org/10.1517/17425255.4.11.1429 PubMedCrossRefGoogle Scholar
  2. Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, McAllister F, Edeal J, Gaus K, Husain S, Kreindler JL, Dubin PJ, Pilewski JM, Myerburg MM, Mason CA, Iwakura Y, Kolls JK (2008) IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 14(3):275–281.  https://doi.org/10.1038/nm1710 PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bae MJ, See HJ, Choi G, Kang CY (2016a) Regulatory T cell induced by Poria cocos bark exert therapeutic effects in murine models of atopic dermatitis and food allergy. Mediators Inflamm 2016:3472608.  https://doi.org/10.1155/2016/3472608 PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bae MJ, Shin HS, See HJ, Jung SY, Kwon DA, Shon DH (2016b) Baicalein induces CD4(+)Foxp3(+) T cells and enhances intestinal barrier function in a mouse model of food allergy. Sci Rep 6:32225.  https://doi.org/10.1038/srep32225 PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bessede A, Gargaro M, Pallotta MT, Matino D, Servillo G, Brunacci C, Bicciato S, Mazza EM, Macchiarulo A, Vacca C, Iannitti R, Tissi L, Volpi C, Belladonna ML, Orabona C, Bianchi R, Lanz TV, Platten M, Della Fazia MA, Piobbico D, Zelante T, Funakoshi H, Nakamura T, Gilot D, Denison MS, Guillemin GJ, DuHadaway JB, Prendergast GC, Metz R, Geffard M, Boon L, Pirro M, Iorio A, Veyret B, Romani L, Grohmann U, Fallarino F, Puccetti P (2014) Aryl hydrocarbon receptor control of a disease tolerance defence pathway. Nature 511(7508):184–190.  https://doi.org/10.1038/nature13323 PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bieber T (2008) Atopic dermatitis. N Engl J Med 358(14):1483–1494.  https://doi.org/10.1056/NEJMra074081 PubMedCrossRefGoogle Scholar
  7. Bock KW, Kohle C (2009) The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver. Biol Chem 390(12):1225–1235.  https://doi.org/10.1515/BC.2009.138 PubMedCrossRefGoogle Scholar
  8. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Camargo CA Jr, Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, Levy BD, Lieberman P, Luccioli S, McCall KM, Schneider LC, Simon RA, Simons FE, Teach SJ, Yawn BP, Schwaninger JM, NIAID-Sponsored Expert Panel (2010) Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-Sponsored Expert Panel report. J Allergy Clin Immunol 126(6):1105–1118.  https://doi.org/10.1016/j.jaci.2010.10.008 PubMedPubMedCentralCrossRefGoogle Scholar
  9. Brauze D, Widerak M, Cwykiel J, Szyfter K, Baer-Dubowska W (2006) The effect of aryl hydrocarbon receptor ligands on the expression of AhR, AhRR, ARNT, Hif1alpha, CYP1A1 and NQO1 genes in rat liver. Toxicol Lett 167(3):212–220.  https://doi.org/10.1016/j.toxlet.2006.09.010 PubMedCrossRefGoogle Scholar
  10. Bunger MK, Glover E, Moran SM, Walisser JA, Lahvis GP, Hsu EL, Bradfield CA (2008) Abnormal liver development and resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in mice carrying a mutation in the DNA-binding domain of the aryl hydrocarbon receptor. Toxicol Sci 106(1):83–92.  https://doi.org/10.1093/toxsci/kfn149 PubMedPubMedCentralCrossRefGoogle Scholar
  11. Carlson DB, Perdew GH (2002) A dynamic role for the Ah receptor in cell signaling? Insights from a diverse group of Ah receptor interacting proteins. J Biochem Mol Toxicol 16(6):317–325.  https://doi.org/10.1002/jbt.10051 PubMedCrossRefGoogle Scholar
  12. Chiaro CR, Patel RD, Marcus CB, Perdew GH (2007) Evidence for an aryl hydrocarbon receptor-mediated cytochrome p450 autoregulatory pathway. Mol Pharmacol 72(5):1369–1379.  https://doi.org/10.1124/mol.107.038968 PubMedCrossRefGoogle Scholar
  13. Chiba T, Uchi H, Tsuji G, Gondo H, Moroi Y, Furue M (2011) Arylhydrocarbon receptor (AhR) activation in airway epithelial cells induces MUC5AC via reactive oxygen species (ROS) production. Pulm Pharmacol Ther 24(1):133–140.  https://doi.org/10.1016/j.pupt.2010.08.002 PubMedCrossRefGoogle Scholar
  14. Denison MS, Nagy SR (2003) Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 43:309–334.  https://doi.org/10.1146/annurev.pharmtox.43.100901.135828 PubMedCrossRefGoogle Scholar
  15. Di Meglio P, Duarte JH, Ahlfors H, Owens ND, Li Y, Villanova F, Tosi I, Hirota K, Nestle FO, Mrowietz U, Gilchrist MJ, Stockinger B (2014) Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions. Immunity 40(6):989–1001.  https://doi.org/10.1016/j.immuni.2014.04.019 PubMedPubMedCentralCrossRefGoogle Scholar
  16. Duarte JH, Di Meglio P, Hirota K, Ahlfors H, Stockinger B (2013) Differential influences of the aryl hydrocarbon receptor on Th17 mediated responses in vitro and in vivo. PLoS One 8(11):e79819.  https://doi.org/10.1371/journal.pone.0079819 PubMedPubMedCentralCrossRefGoogle Scholar
  17. Esser C, Rannug A (2015) The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol Rev 67(2):259–279.  https://doi.org/10.1124/pr.114.009001 PubMedCrossRefGoogle Scholar
  18. Esser C, Bargen I, Weighardt H, Haarmann-Stemmann T, Krutmann J (2013) Functions of the aryl hydrocarbon receptor in the skin. Semin Immunopathol 35(6):677–691.  https://doi.org/10.1007/s00281-013-0394-4 PubMedCrossRefGoogle Scholar
  19. Fernandez-Salguero PM, Ward JM, Sundberg JP, Gonzalez FJ (1997) Lesions of aryl-hydrocarbon receptor-deficient mice. Vet Pathol 34(6):605–614.  https://doi.org/10.1177/030098589703400609 PubMedCrossRefGoogle Scholar
  20. Fujii-Kuriyama Y, Mimura J (2005) Molecular mechanisms of AhR functions in the regulation of cytochrome P450 genes. Biochem Biophys Res Commun 338(1):311–317.  https://doi.org/10.1016/j.bbrc.2005.08.162 PubMedCrossRefGoogle Scholar
  21. Fujita H, Soyka MB, Akdis M, Akdis CA (2012) Mechanisms of allergen-specific immunotherapy. Clin Transl Allergy 2(1):2.  https://doi.org/10.1186/2045-7022-2-2 PubMedPubMedCentralCrossRefGoogle Scholar
  22. Gilfillan AM, Tkaczyk C (2006) Integrated signalling pathways for mast-cell activation. Nat Rev Immunol 6(3):218–230.  https://doi.org/10.1038/nri1782 PubMedCrossRefGoogle Scholar
  23. Guyot E, Chevallier A, Barouki R, Coumoul X (2013) The AhR twist: ligand-dependent AhR signaling and pharmaco-toxicological implications. Drug Discov Today 18(9–10):479–486.  https://doi.org/10.1016/j.drudis.2012.11.014 PubMedCrossRefGoogle Scholar
  24. Haarmann-Stemmann T, Esser C, Krutmann J (2015) The janus-faced role of aryl hydrocarbon receptor signaling in the skin: consequences for prevention and treatment of skin disorders. J Invest Dermatol 135(11):2572–2576.  https://doi.org/10.1038/jid.2015.285 PubMedCrossRefGoogle Scholar
  25. Hahn ME (2002) Aryl hydrocarbon receptors: diversity and evolution. Chem Biol Interact 141(1–2):131–160PubMedCrossRefGoogle Scholar
  26. Hahn ME, Allan LL, Sherr DH (2009) Regulation of constitutive and inducible AHR signaling: complex interactions involving the AHR repressor. Biochem Pharmacol 77(4):485–497.  https://doi.org/10.1016/j.bcp.2008.09.016 PubMedCrossRefGoogle Scholar
  27. Hahn ME, Karchner SI, Merson RR (2017) Diversity as opportunity: insights from 600 million years of AHR evolution. Curr Opin Toxicol 2:58–71.  https://doi.org/10.1016/j.cotox.2017.02.003 PubMedCrossRefGoogle Scholar
  28. Hakim-Rad K, Metz M, Maurer M (2009) Mast cells: makers and breakers of allergic inflammation. Curr Opin Allergy Clin Immunol 9(5):427–430.  https://doi.org/10.1097/ACI.0b013e32832e9af1 PubMedCrossRefGoogle Scholar
  29. Hankinson O (1995) The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 35:307–340.  https://doi.org/10.1146/annurev.pa.35.040195.001515 PubMedCrossRefGoogle Scholar
  30. Hanlon PR, Ganem LG, Cho YC, Yamamoto M, Jefcoate CR (2003) AhR- and ERK-dependent pathways function synergistically to mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin suppression of peroxisome proliferator-activated receptor-gamma1 expression and subsequent adipocyte differentiation. Toxicol Appl Pharmacol 189(1):11–27PubMedCrossRefGoogle Scholar
  31. Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479.  https://doi.org/10.1146/annurev.biochem.67.1.425 PubMedCrossRefGoogle Scholar
  32. Hidaka T, Ogawa E, Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Fujimura T, Aiba S, Nakayama K, Okuyama R, Yamamoto M (2017) The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin. Nat Immunol 18(1):64–73.  https://doi.org/10.1038/ni.3614 PubMedCrossRefGoogle Scholar
  33. Hoffer A, Chang CY, Puga A (1996) Dioxin induces transcription of fos and jun genes by Ah receptor-dependent and -independent pathways. Toxicol Appl Pharmacol 141(1):238–247.  https://doi.org/10.1006/taap.1996.0280 PubMedCrossRefGoogle Scholar
  34. Hong CH, Lee CH, Yu HS, Huang SK (2016) Benzopyrene, a major polyaromatic hydrocarbon in smoke fume, mobilizes Langerhans cells and polarizes Th2/17 responses in epicutaneous protein sensitization through the aryl hydrocarbon receptor. Int Immunopharmacol 36:111–117.  https://doi.org/10.1016/j.intimp.2016.04.017 PubMedCrossRefGoogle Scholar
  35. Hwang JA, Lee JA, Cheong SW, Youn HJ, Park JH (2007) Benzo(a)pyrene inhibits growth and functional differentiation of mouse bone marrow-derived dendritic cells. Downregulation of RelB and eIF3 p170 by benzo(a)pyrene. Toxicol Lett 169(1):82–90.  https://doi.org/10.1016/j.toxlet.2007.01.001 PubMedCrossRefGoogle Scholar
  36. Hwang YJ, Yun MO, Jeong KT, Park JH (2014) Uremic toxin indoxyl 3-sulfate regulates the differentiation of Th2 but not of Th1 cells to lessen allergic asthma. Toxicol Lett 225(1):130–138.  https://doi.org/10.1016/j.toxlet.2013.11.027 PubMedCrossRefGoogle Scholar
  37. Ikuta T, Kobayashi Y, Kawajiri K (2004) Cell density regulates intracellular localization of aryl hydrocarbon receptor. J Biol Chem 279(18):19209–19216.  https://doi.org/10.1074/jbc.M310492200 PubMedCrossRefGoogle Scholar
  38. Issemann I, Green S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347(6294):645–650.  https://doi.org/10.1038/347645a0 PubMedCrossRefGoogle Scholar
  39. Jeon MS, Esser C (2000) The murine IL-2 promoter contains distal regulatory elements responsive to the Ah receptor, a member of the evolutionarily conserved bHLH-PAS transcription factor family. J Immunol 165(12):6975–6983PubMedCrossRefGoogle Scholar
  40. Jeong KT, Hwang SJ, Oh GS, Park JH (2012) FICZ, a tryptophan photoproduct, suppresses pulmonary eosinophilia and Th2-type cytokine production in a mouse model of ovalbumin-induced allergic asthma. Int Immunopharmacol 13(4):377–385.  https://doi.org/10.1016/j.intimp.2012.04.014 PubMedCrossRefGoogle Scholar
  41. Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, Ebmeier CC, Goossens J, Rahl PB, Levine SS, Taatjes DJ, Dekker J, Young RA (2010) Mediator and cohesin connect gene expression and chromatin architecture. Nature 467(7314):430–435.  https://doi.org/10.1038/nature09380 PubMedPubMedCentralCrossRefGoogle Scholar
  42. Karchner SI, Franks DG, Kennedy SW, Hahn ME (2006) The molecular basis for differential dioxin sensitivity in birds: role of the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 103(16):6252–6257.  https://doi.org/10.1073/pnas.0509950103 PubMedPubMedCentralCrossRefGoogle Scholar
  43. Kerkvliet NI, Shepherd DM, Baecher-Steppan L (2002) T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD. Toxicol Appl Pharmacol 185(2):146–152PubMedCrossRefGoogle Scholar
  44. Kewley RJ, Whitelaw ML, Chapman-Smith A (2004) The mammalian basic helix-loop-helix/PAS family of transcriptional regulators. Int J Biochem Cell Biol 36(2):189–204PubMedCrossRefGoogle Scholar
  45. Kiss EA, Vonarbourg C, Kopfmann S, Hobeika E, Finke D, Esser C, Diefenbach A (2011) Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334(6062):1561–1565.  https://doi.org/10.1126/science.1214914 PubMedCrossRefGoogle Scholar
  46. Koch S, Stroisch TJ, Vorac J, Herrmann N, Leib N, Schnautz S, Kirins H, Forster I, Weighardt H, Bieber T (2017) AhR mediates an anti-inflammatory feed-back mechanism in human Langerhans cells involving FcepsilonRI and IDO. Allergy 72(11):1686–1693.  https://doi.org/10.1111/all.13170 PubMedCrossRefGoogle Scholar
  47. Kronenberg S, Esser C, Carlberg C (2000) An aryl hydrocarbon receptor conformation acts as the functional core of nuclear dioxin signaling. Nucleic Acids Res 28(12):2286–2291PubMedPubMedCentralCrossRefGoogle Scholar
  48. Lawrence BP, Denison MS, Novak H, Vorderstrasse BA, Harrer N, Neruda W, Reichel C, Woisetschlager M (2008) Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound. Blood 112(4):1158–1165.  https://doi.org/10.1182/blood-2007-08-109645 PubMedPubMedCentralCrossRefGoogle Scholar
  49. Lee JS, Cella M, McDonald KG, Garlanda C, Kennedy GD, Nukaya M, Mantovani A, Kopan R, Bradfield CA, Newberry RD, Colonna M (2012) AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat Immunol 13(2):144–151.  https://doi.org/10.1038/ni.2187 CrossRefGoogle Scholar
  50. Li W, Matsumura F (2008) Significance of the nongenomic, inflammatory pathway in mediating the toxic action of TCDD to induce rapid and long-term cellular responses in 3T3-L1 adipocytes. Biochemistry 47(52):13997–14008.  https://doi.org/10.1021/bi801913w PubMedCrossRefGoogle Scholar
  51. Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR, Grigorieva EF, Wilhelm C, Veldhoen M (2011) Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147(3):629–640.  https://doi.org/10.1016/j.cell.2011.09.025 PubMedCrossRefGoogle Scholar
  52. Li XM, Peng J, Gu W, Guo XJ (2016) TCDD-induced activation of aryl hydrocarbon receptor inhibits Th17 polarization and regulates non-eosinophilic airway inflammation in asthma. PLoS One 11(3):e0150551.  https://doi.org/10.1371/journal.pone.0150551 PubMedPubMedCentralCrossRefGoogle Scholar
  53. Loub WD, Wattenberg LW, Davis DW (1975) Aryl hydrocarbon hydroxylase induction in rat tissues by naturally occurring indoles of cruciferous plants. J Natl Cancer Inst 54(4):985–988PubMedGoogle Scholar
  54. Ma Q, Baldwin KT (2000) 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced degradation of aryl hydrocarbon receptor (AhR) by the ubiquitin-proteasome pathway. Role of the transcription activaton and DNA binding of AhR. J Biol Chem 275(12):8432–8438PubMedCrossRefGoogle Scholar
  55. Machado FS, Johndrow JE, Esper L, Dias A, Bafica A, Serhan CN, Aliberti J (2006) Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Nat Med 12(3):330–334.  https://doi.org/10.1038/nm1355 PubMedCrossRefGoogle Scholar
  56. Marlowe JL, Fan Y, Chang X, Peng L, Knudsen ES, Xia Y, Puga A (2008) The aryl hydrocarbon receptor binds to E2F1 and inhibits E2F1-induced apoptosis. Mol Biol Cell 19(8):3263–3271.  https://doi.org/10.1091/mbc.E08-04-0359 PubMedPubMedCentralCrossRefGoogle Scholar
  57. Marshall NB, Kerkvliet NI (2010) Dioxin and immune regulation: emerging role of aryl hydrocarbon receptor in the generation of regulatory T cells. Ann NY Acad Sci 1183:25–37.  https://doi.org/10.1111/j.1749-6632.2009.05125.x PubMedPubMedCentralCrossRefGoogle Scholar
  58. Matsumura F (2009) The significance of the nongenomic pathway in mediating inflammatory signaling of the dioxin-activated Ah receptor to cause toxic effects. Biochem Pharmacol 77(4):608–626.  https://doi.org/10.1016/j.bcp.2008.10.013 PubMedCrossRefGoogle Scholar
  59. McMillan BJ, Bradfield CA (2007) The aryl hydrocarbon receptor is activated by modified low-density lipoprotein. Proc Natl Acad Sci USA 104(4):1412–1417.  https://doi.org/10.1073/pnas.0607296104 PubMedPubMedCentralCrossRefGoogle Scholar
  60. Mexia N, Gaitanis G, Velegraki A, Soshilov A, Denison MS, Magiatis P (2015) Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast. Arch Biochem Biophys 571:16–20.  https://doi.org/10.1016/j.abb.2015.02.023 PubMedPubMedCentralCrossRefGoogle Scholar
  61. Mimura J, Fujii-Kuriyama Y (2003) Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta 1619(3):263–268PubMedCrossRefGoogle Scholar
  62. Neff-LaFord H, Teske S, Bushnell TP, Lawrence BP (2007) Aryl hydrocarbon receptor activation during influenza virus infection unveils a novel pathway of IFN-gamma production by phagocytic cells. J Immunol 179(1):247–255PubMedCrossRefGoogle Scholar
  63. Negishi T, Kato Y, Ooneda O, Mimura J, Takada T, Mochizuki H, Yamamoto M, Fujii-Kuriyama Y, Furusako S (2005) Effects of aryl hydrocarbon receptor signaling on the modulation of TH1/TH2 balance. J Immunol 175(11):7348–7356PubMedCrossRefGoogle Scholar
  64. Nguyen LP, Bradfield CA (2008) The search for endogenous activators of the aryl hydrocarbon receptor. Chem Res Toxicol 21(1):102–116.  https://doi.org/10.1021/tx7001965 PubMedCrossRefGoogle Scholar
  65. Nguyen LP, Hsu EL, Chowdhury G, Dostalek M, Guengerich FP, Bradfield CA (2009) D-amino acid oxidase generates agonists of the aryl hydrocarbon receptor from D-tryptophan. Chem Res Toxicol 22(12):1897–1904.  https://doi.org/10.1021/tx900043s PubMedPubMedCentralCrossRefGoogle Scholar
  66. Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, Ramon M, Bergman R, Krueger JG, Guttman-Yassky E (2009) IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 123(6):1244–1252.e1242.  https://doi.org/10.1016/j.jaci.2009.03.041 PubMedPubMedCentralCrossRefGoogle Scholar
  67. Nuti R, Gargaro M, Matino D, Dolciami D, Grohmann U, Puccetti P, Fallarino F, Macchiarulo A (2014) Ligand binding and functional selectivity of L-tryptophan metabolites at the mouse aryl hydrocarbon receptor (mAhR). J Chem Inf Model 54(12):3373–3383.  https://doi.org/10.1021/ci5005459 PubMedCrossRefGoogle Scholar
  68. Oesch-Bartlomowicz B, Huelster A, Wiss O, Antoniou-Lipfert P, Dietrich C, Arand M, Weiss C, Bockamp E, Oesch F (2005) Aryl hydrocarbon receptor activation by cAMP vs. dioxin: divergent signaling pathways. Proc Natl Acad Sci USA 102(26):9218–9223.  https://doi.org/10.1073/pnas.0503488102 PubMedPubMedCentralCrossRefGoogle Scholar
  69. Ohtake F, Baba A, Takada I, Okada M, Iwasaki K, Miki H, Takahashi S, Kouzmenko A, Nohara K, Chiba T, Fujii-Kuriyama Y, Kato S (2007) Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 446(7135):562–566.  https://doi.org/10.1038/nature05683 PubMedCrossRefGoogle Scholar
  70. Okino ST, Whitlock JP Jr (1995) Dioxin induces localized, graded changes in chromatin structure: implications for Cyp1A1 gene transcription. Mol Cell Biol 15(7):3714–3721PubMedPubMedCentralCrossRefGoogle Scholar
  71. Ple C, Fan Y, Ait Yahia S, Vorng H, Everaere L, Chenivesse C, Balsamelli J, Azzaoui I, de Nadai P, Wallaert B, Lazennec G, Tsicopoulos A (2015) Polycyclic aromatic hydrocarbons reciprocally regulate IL-22 and IL-17 cytokines in peripheral blood mononuclear cells from both healthy and asthmatic subjects. PLoS One 10(4):e0122372.  https://doi.org/10.1371/journal.pone.0122372 PubMedPubMedCentralCrossRefGoogle Scholar
  72. Pollenz RS, Buggy C (2006) Ligand-dependent and -independent degradation of the human aryl hydrocarbon receptor (hAHR) in cell culture models. Chem Biol Interact 164(1–2):49–59.  https://doi.org/10.1016/j.cbi.2006.08.014 PubMedCrossRefGoogle Scholar
  73. Puga A, Barnes SJ, Dalton TP, Chang C, Knudsen ES, Maier MA (2000) Aromatic hydrocarbon receptor interaction with the retinoblastoma protein potentiates repression of E2F-dependent transcription and cell cycle arrest. J Biol Chem 275(4):2943–2950PubMedCrossRefGoogle Scholar
  74. Puga A, Ma C, Marlowe JL (2009) The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways. Biochem Pharmacol 77(4):713–722.  https://doi.org/10.1016/j.bcp.2008.08.031 PubMedCrossRefGoogle Scholar
  75. Quintana FJ (2013) The aryl hydrocarbon receptor: a molecular pathway for the environmental control of the immune response. Immunology 138(3):183–189.  https://doi.org/10.1111/imm.12046 PubMedPubMedCentralCrossRefGoogle Scholar
  76. Quintana FJ, Sherr DH (2013) Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol Rev 65(4):1148–1161.  https://doi.org/10.1124/pr.113.007823 PubMedPubMedCentralCrossRefGoogle Scholar
  77. Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL (2008) Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453(7191):65–71.  https://doi.org/10.1038/nature06880 PubMedCrossRefGoogle Scholar
  78. Ruby CE, Leid M, Kerkvliet NI (2002) 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-alpha and anti-CD40-induced activation of NF-kappaB/Rel in dendritic cells: p50 homodimer activation is not affected. Mol Pharmacol 62(3):722–728PubMedCrossRefGoogle Scholar
  79. Schroeder JC, Dinatale BC, Murray IA, Flaveny CA, Liu Q, Laurenzana EM, Lin JM, Strom SC, Omiecinski CJ, Amin S, Perdew GH (2010) The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry 49(2):393–400.  https://doi.org/10.1021/bi901786x PubMedPubMedCentralCrossRefGoogle Scholar
  80. Schulz VJ, Smit JJ, Willemsen KJ, Fiechter D, Hassing I, Bleumink R, Boon L, van den Berg M, van Duursen MB, Pieters RH (2011) Activation of the aryl hydrocarbon receptor suppresses sensitization in a mouse peanut allergy model. Toxicol Sci 123(2):491–500.  https://doi.org/10.1093/toxsci/kfr175 PubMedCrossRefGoogle Scholar
  81. Schulz VJ, Smit JJ, Bol-Schoenmakers M, van Duursen MB, van den Berg M, Pieters RH (2012a) Activation of the aryl hydrocarbon receptor reduces the number of precursor and effector T cells, but preserves thymic CD4+CD25+Foxp3+ regulatory T cells. Toxicol Lett 215(2):100–109.  https://doi.org/10.1016/j.toxlet.2012.09.024 PubMedCrossRefGoogle Scholar
  82. Schulz VJ, Smit JJ, Huijgen V, Bol-Schoenmakers M, van Roest M, Kruijssen LJ, Fiechter D, Hassing I, Bleumink R, Safe S, van Duursen MB, van den Berg M, Pieters RH (2012b) Non-dioxin-like AhR ligands in a mouse peanut allergy model. Toxicol Sci 128(1):92–102.  https://doi.org/10.1093/toxsci/kfs131 PubMedCrossRefGoogle Scholar
  83. Schulz VJ, van Roest M, Bol-Schoenmakers M, van Duursen MB, van den Berg M, Pieters RH, Smit JJ (2013) Aryl hydrocarbon receptor activation affects the dendritic cell phenotype and function during allergic sensitization. Immunobiology 218(8):1055–1062.  https://doi.org/10.1016/j.imbio.2013.01.004 PubMedCrossRefGoogle Scholar
  84. Sciullo EM, Vogel CF, Li W, Matsumura F (2008) Initial and extended inflammatory messages of the nongenomic signaling pathway of the TCDD-activated Ah receptor in U937 macrophages. Arch Biochem Biophys 480(2):143–155.  https://doi.org/10.1016/j.abb.2008.09.017 PubMedCrossRefGoogle Scholar
  85. Sibilano R, Frossi B, Calvaruso M, Danelli L, Betto E, Dall’Agnese A, Tripodo C, Colombo MP, Pucillo CE, Gri G (2012) The aryl hydrocarbon receptor modulates acute and late mast cell responses. J Immunol 189(1):120–127.  https://doi.org/10.4049/jimmunol.1200009 PubMedCrossRefGoogle Scholar
  86. Sicherer SH, Sampson HA (2010) Food allergy. J Allergy Clin Immunol 125(2 Suppl 2):S116–S125.  https://doi.org/10.1016/j.jaci.2009.08.028 PubMedCrossRefGoogle Scholar
  87. Simonian PL, Wehrmann F, Roark CL, Born WK, O’Brien RL, Fontenot AP (2010) Gammadelta T cells protect against lung fibrosis via IL-22. J Exp Med 207(10):2239–2253.  https://doi.org/10.1084/jem.20100061 PubMedPubMedCentralCrossRefGoogle Scholar
  88. Sogawa K, Fujii-Kuriyama Y (1997) Ah receptor, a novel ligand-activated transcription factor. J Biochem 122(6):1075–1079PubMedCrossRefGoogle Scholar
  89. Song J, Clagett-Dame M, Peterson RE, Hahn ME, Westler WM, Sicinski RR, DeLuca HF (2002) A ligand for the aryl hydrocarbon receptor isolated from lung. Proc Natl Acad Sci USA 99(23):14694–14699.  https://doi.org/10.1073/pnas.232562899 PubMedPubMedCentralCrossRefGoogle Scholar
  90. Stange J, Veldhoen M (2013) The aryl hydrocarbon receptor in innate T cell immunity. Semin Immunopathol 35(6):645–655.  https://doi.org/10.1007/s00281-013-0389-1 PubMedCrossRefGoogle Scholar
  91. Suen JL, Hsu SH, Hung CH, Chao YS, Lee CL, Lin CY, Weng TH, Yu HS, Huang SK (2013) A common environmental pollutant, 4-nonylphenol, promotes allergic lung inflammation in a murine model of asthma. Allergy 68(6):780–787.  https://doi.org/10.1111/all.12156 PubMedCrossRefGoogle Scholar
  92. Tauchi M, Hida A, Negishi T, Katsuoka F, Noda S, Mimura J, Hosoya T, Yanaka A, Aburatani H, Fujii-Kuriyama Y, Motohashi H, Yamamoto M (2005) Constitutive expression of aryl hydrocarbon receptor in keratinocytes causes inflammatory skin lesions. Mol Cell Biol 25(21):9360–9368.  https://doi.org/10.1128/MCB.25.21.9360-9368.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  93. Teske S, Bohn AA, Regal JF, Neumiller JJ, Lawrence BP (2005) Activation of the aryl hydrocarbon receptor increases pulmonary neutrophilia and diminishes host resistance to influenza A virus. Am J Physiol Lung Cell Mol Physiol 289(1):L111–L124.  https://doi.org/10.1152/ajplung.00318.2004 PubMedCrossRefGoogle Scholar
  94. Thatcher TH, Williams MA, Pollock SJ, McCarthy CE, Lacy SH, Phipps RP, Sime PJ (2016) Endogenous ligands of the aryl hydrocarbon receptor regulate lung dendritic cell function. Immunology 147(1):41–54.  https://doi.org/10.1111/imm.12540 PubMedCrossRefGoogle Scholar
  95. Tian Y (2009) Ah receptor and NF-kappaB interplay on the stage of epigenome. Biochem Pharmacol 77(4):670–680.  https://doi.org/10.1016/j.bcp.2008.10.023 PubMedCrossRefGoogle Scholar
  96. Tian Y, Ke S, Chen M, Sheng T (2003) Interactions between the aryl hydrocarbon receptor and P-TEFb. Sequential recruitment of transcription factors and differential phosphorylation of C-terminal domain of RNA polymerase II at cyp1a1 promoter. J Biol Chem 278(45):44041–44048.  https://doi.org/10.1074/jbc.M306443200 PubMedCrossRefGoogle Scholar
  97. Tian J, Feng Y, Fu H, Xie HQ, Jiang JX, Zhao B (2015) The aryl hydrocarbon receptor: a key bridging molecule of external and internal chemical signals. Environ Sci Technol 49(16):9518–9531.  https://doi.org/10.1021/acs.est.5b00385 PubMedPubMedCentralCrossRefGoogle Scholar
  98. Torgerson TR, Linane A, Moes N, Anover S, Mateo V, Rieux-Laucat F, Hermine O, Vijay S, Gambineri E, Cerf-Bensussan N, Fischer A, Ochs HD, Goulet O, Ruemmele FM (2007) Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 gene. Gastroenterology 132(5):1705–1717.  https://doi.org/10.1053/j.gastro.2007.02.044 PubMedCrossRefGoogle Scholar
  99. Tsai MJ, Hsu YL, Wang TN, Wu LY, Lien CT, Hung CH, Kuo PL, Huang MS (2014) Aryl hydrocarbon receptor (AhR) agonists increase airway epithelial matrix metalloproteinase activity. J Mol Med 92(6):615–628.  https://doi.org/10.1007/s00109-014-1121-x PubMedCrossRefGoogle Scholar
  100. Tsai MJ, Wang TN, Lin YS, Kuo PL, Hsu YL, Huang MS (2015) Aryl hydrocarbon receptor agonists upregulate VEGF secretion from bronchial epithelial cells. J Mol Med 93(11):1257–1269.  https://doi.org/10.1007/s00109-015-1304-0 PubMedCrossRefGoogle Scholar
  101. van den Bogaard EH, Bergboer JG, Vonk-Bergers M, van Vlijmen-Willems IM, Hato SV, van der Valk PG, Schroder JM, Joosten I, Zeeuwen PL, Schalkwijk J (2013) Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis. J Clin Invest 123(2):917–927.  https://doi.org/10.1172/JCI65642 PubMedPubMedCentralGoogle Scholar
  102. Vogel CF, Sciullo E, Li W, Wong P, Lazennec G, Matsumura F (2007) RelB, a new partner of aryl hydrocarbon receptor-mediated transcription. Mol Endocrinol 21(12):2941–2955.  https://doi.org/10.1210/me.2007-0211 PubMedPubMedCentralCrossRefGoogle Scholar
  103. Vogel CF, Goth SR, Dong B, Pessah IN, Matsumura F (2008) Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun 375(3):331–335.  https://doi.org/10.1016/j.bbrc.2008.07.156 PubMedPubMedCentralCrossRefGoogle Scholar
  104. Wang S, Hankinson O (2002) Functional involvement of the Brahma/SWI2-related gene 1 protein in cytochrome P4501A1 transcription mediated by the aryl hydrocarbon receptor complex. J Biol Chem 277(14):11821–11827.  https://doi.org/10.1074/jbc.M110122200 PubMedCrossRefGoogle Scholar
  105. Wang S, Ge K, Roeder RG, Hankinson O (2004) Role of mediator in transcriptional activation by the aryl hydrocarbon receptor. J Biol Chem 279(14):13593–13600.  https://doi.org/10.1074/jbc.M312274200 PubMedCrossRefGoogle Scholar
  106. Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K, Volk HD, Sterry W, Sabat R (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36(5):1309–1323.  https://doi.org/10.1002/eji.200535503 PubMedCrossRefGoogle Scholar
  107. Wong PS, Vogel CF, Kokosinski K, Matsumura F (2010) Arylhydrocarbon receptor activation in NCI-H441 cells and C57BL/6 mice: possible mechanisms for lung dysfunction. Am J Respir Cell Mol Biol 42(2):210–217.  https://doi.org/10.1165/rcmb.2008-0228OC PubMedCrossRefGoogle Scholar
  108. Wu HY, Quintana FJ, da Cunha AP, Dake BT, Koeglsperger T, Starossom SC, Weiner HL (2011) In vivo induction of Tr1 cells via mucosal dendritic cells and AHR signaling. PLoS One 6(8):e23618.  https://doi.org/10.1371/journal.pone.0023618 PubMedPubMedCentralCrossRefGoogle Scholar
  109. Xia M, Viera-Hutchins L, Garcia-Lloret M, Noval Rivas M, Wise P, McGhee SA, Chatila ZK, Daher N, Sioutas C, Chatila TA (2015) Vehicular exhaust particles promote allergic airway inflammation through an aryl hydrocarbon receptor-notch signaling cascade. J Allergy Clin Immunol 136(2):441–453.  https://doi.org/10.1016/j.jaci.2015.02.014 PubMedPubMedCentralCrossRefGoogle Scholar
  110. Yin H, Li Y, Sutter TR (1994) Dioxin-enhanced expression of interleukin-1 beta in human epidermal keratinocytes: potential role in the modulation of immune and inflammatory responses. Exp Clin Immunogenet 11(2–3):128–135PubMedGoogle Scholar
  111. Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, Zecchi R, D’Angelo C, Massi-Benedetti C, Fallarino F, Carvalho A, Puccetti P, Romani L (2013) Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39(2):372–385.  https://doi.org/10.1016/j.immuni.2013.08.003 PubMedCrossRefGoogle Scholar
  112. Zhou Y, Tung HY, Tsai YM, Hsu SC, Chang HW, Kawasaki H, Tseng HC, Plunkett B, Gao P, Hung CH, Vonakis BM, Huang SK (2013) Aryl hydrocarbon receptor controls murine mast cell homeostasis. Blood 121(16):3195–3204.  https://doi.org/10.1182/blood-2012-08-453597 PubMedPubMedCentralCrossRefGoogle Scholar
  113. Zhou Y, Mirza S, Xu T, Tripathi P, Plunkett B, Myers A, Gao P (2014) Aryl hydrocarbon receptor (AhR) modulates cockroach allergen-induced immune responses through active TGFbeta1 release. Mediat Inflamm 2014:591479.  https://doi.org/10.1155/2014/591479 Google Scholar
  114. Zhu J, Cao Y, Li K, Wang Z, Zuo P, Xiong W, Xu Y, Xiong S (2011) Increased expression of aryl hydrocarbon receptor and interleukin 22 in patients with allergic asthma. Asian Pac J Allergy Immunol 29(3):266–272PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Marco Gargaro
    • 1
  • Matteo Pirro
    • 2
  • Giorgia Manni
    • 1
  • Antonella De Luca
    • 1
  • Teresa Zelante
    • 1
  • Francesca Fallarino
    • 1
    Email author
  1. 1.Department of Experimental MedicineUniversity of PerugiaPerugiaItaly
  2. 2.Department of MedicineUniversity of PerugiaPerugiaItaly

Personalised recommendations