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Review Article

The tryptophan derivative 6-formylindolo[3,2-b]carbazole, FICZ, a dynamic mediator of endogenous aryl hydrocarbon receptor signaling, balances cell growth and differentiation

ORCID Icon & ORCID Icon
Pages 555-574 | Received 04 May 2018, Accepted 21 Jun 2018, Published online: 18 Sep 2018

References

  • Abbott BD, Schmid JE, Pitt JA, Buckalew AR, Wood CR, Held GA, Diliberto JJ. 1999. Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse. Toxicol Appl Pharmacol. 155:62–70.
  • Abu-Rezq HA, Millar DG. 2013. Streptozotocin-induced diabetes depends on the balance of Th17/Treg responses and is modulated by ligands of the aryl-hydrocarbon receptor. Int J Immunol Res. 3:40–49.
  • Adachi J, Mori Y, Matsui S, Takigami H, Fujino J, Kitagawa H, Miller CA III, Kato T, Saeki K, Matsuda T. 2001. Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine. J Biol Chem. 276:31475–31478.
  • Afaq F, Zaid MA, Pelle E, Khan N, Syed DN, Matsui MS, Maes D, Mukhtar H. 2009. Aryl hydrocarbon receptor is an ozone sensor in human skin. J Invest Dermatol. 129:2396–2403.
  • Apetoh L, Quintana FJ, Pot C, Joller N, Xiao S, Kumar D, Burns EJ, Sherr DH, Weiner HL, Kuchroo VK. 2010. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat Immunol. 11:854–861.
  • Ash PEA, Stanford EA, Al Abdulatif A, Ramirez-Cardenas A, Ballance HI, Boudeau S, Jeh A, Murithi JM, Tripodis Y, Murphy GJ, et al. 2017. Dioxins and related environmental contaminants increase TDP-43 levels. Mol Neurodegener. 12:35.
  • Ashbee HR. 2006. Recent developments in the immunology and biology of Malassezia species. FEMS Immunol Med Microbiol. 47:14–23.
  • Baba T, Mimura J, Nakamura N, Harada N, Yamamoto M, Morohashi K, Fujii-Kuriyama Y. 2005. Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction. Mol Cell Biol. 25:10040–10051.
  • Baba T, Shima Y, Owaki A, Mimura J, Oshima M, Fujii-Kuriyama Y, Morohashi KI. 2008. Disruption of aryl hydrocarbon receptor (AhR) induces regression of the seminal vesicle in aged male mice. Sex Dev. 2:1–11.
  • Bankoti J, Rase B, Simones T, Shepherd DM. 2010. Functional and phenotypic effects of AhR activation in inflammatory dendritic cells. Toxicol Appl Pharmacol. 246:18–28.
  • Baron JM, Zwadlo-Klarwasser G, Jugert F, Hamann W, Rubben A, Mukhtar H, Merk HF. 1998. Cytochrome P450 1B1: a major P450 isoenzyme in human blood monocytes and macrophage subsets. Biochem Pharmacol. 56:1105–1110.
  • Beischlag TV, Luis Morales J, Hollingshead BD, Perdew GH. 2008. The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr. 18:207–250.
  • Benedict JC, Lin TM, Loeffler IK, Peterson RE, Flaws JA. 2000. Physiological role of the aryl hydrocarbon receptor in mouse ovary development. Toxicol Sci. 56:382–388.
  • Bennett JA, Singh KP, Unnisa Z, Welle SL, Gasiewicz TA. 2015. Deficiency in aryl hydrocarbon receptor (AHR) expression throughout aging alters gene expression profiles in murine long-term hematopoietic stem cells. PLoS One. 10:e0133791.
  • Bergander L, Wahlstrom N, Alsberg T, Bergman J, Rannug A, Rannug U. 2003. Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole by liquid chromatography-mass spectrometry and NMR. Drug Metab Dispos. 31:233–241.
  • Bergander L, Wincent E, Rannug A, Foroozesh M, Alworth W, Rannug U. 2004. Metabolic fate of the Ah receptor ligand 6-formylindolo[3,2-b]carbazole. Chem Biol Interact. 149:151–164.
  • Bessede A, Gargaro M, Pallotta MT, Matino D, Servillo G, Brunacci C, Bicciato S, Mazza EM, Macchiarulo A, Vacca C, et al. 2014. Aryl hydrocarbon receptor control of a disease tolerance defence pathway. Nature. 511:184–190.
  • Bisson WH, Koch DC, O'Donnell EF, Khalil SM, Kerkvliet NI, Tanguay RL, Abagyan R, Kolluri SK. 2009. Modeling of the aryl hydrocarbon receptor (AhR) ligand binding domain and its utility in virtual ligand screening to predict new AhR ligands. J Med Chem. 52:5635–5641.
  • Bittinger MA, Nguyen LP, Bradfield CA. 2003. Aspartate aminotransferase generates proagonists of the aryl hydrocarbon receptor. Mol Pharmacol. 64:550–556.
  • Bjeldanes LF, Kim JY, Grose KR, Bartholomew JC, Bradfield CA. 1991. 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 USA. 88:9543–9547.
  • Boitano AE, Wang J, Romeo R, Bouchez LC, Parker AE, Sutton SE, Walker JR, Flaveny CA, Perdew GH, Denison MS, et al. 2010. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science. 329:1345–1348.
  • Boule LA, Burke CG, Jin GB, Lawrence BP. 2018. Aryl hydrocarbon receptor signaling modulates antiviral immune responses: ligand metabolism rather than chemical source is the stronger predictor of outcome. Sci Rep. 8:1826.
  • Brem R, Macpherson P, Guven M, Karran P. 2017. Oxidative stress induced by UVA photoactivation of the tryptophan UVB photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) inhibits nucleotide excision repair in human cells. Sci Rep. 7:4310.
  • Bunaciu RP, Jensen HA, MacDonald RJ, LaTocha DH, Varner JD, Yen A. 2015. 6-Formylindolo(3,2-b)carbazole (FICZ) modulates the signalsome responsible for RA-induced differentiation of HL-60 myeloblastic leukemia cells. PLoS One. 10:e0135668.
  • Bunaciu RP, Yen A. 2013. 6-Formylindolo (3,2-b)carbazole (FICZ) enhances retinoic acid (RA)-induced differentiation of HL-60 myeloblastic leukemia cells. Mol Cancer. 12:39.
  • Bunaciu RP, Yen A. 2011. Activation of the aryl hydrocarbon receptor AhR Promotes retinoic acid-induced differentiation of myeloblastic leukemia cells by restricting expression of the stem cell transcription factor Oct4. Cancer Res. 71:2371–2380.
  • Campbell SJ, Henderson CJ, Anthony DC, Davidson D, Clark AJ, Wolf CR. 2005. The murine Cyp1a1 gene is expressed in a restricted spatial and temporal pattern during embryonic development. J Biol Chem. 280:5828–5835.
  • Carmona-Antonanzas G, Santi M, Migaud H, Vera LM. 2017. Light- and clock-control of genes involved in detoxification. Chronobiol Int. 34:1026–1041.
  • Casado FL, Singh KP, Gasiewicz TA. 2011. Aryl hydrocarbon receptor activation in hematopoietic stem/progenitor cells alters cell function and pathway-specific gene modulation reflecting changes in cellular trafficking and migration. Mol Pharmacol. 80:673–682.
  • Chang CY, Puga A. 1998. Constitutive activation of the aromatic hydrocarbon receptor. Mol Cell Biol. 18:525–535.
  • Chang X, Fan Y, Karyala S, Schwemberger S, Tomlinson CR, Sartor MA, Puga A. 2007. Ligand-independent regulation of transforming growth factor beta1 expression and cell cycle progression by the aryl hydrocarbon receptor. Mol Cell Biol. 27:6127–6139.
  • Chen W, Pu A, Sheng B, Zhang Z, Li L, Liu Z, Wang Q, Li X, Ma Y, Yu M, et al. 2017. Aryl hydrocarbon receptor activation modulates CD8alphaalpha + TCRalphabeta + IELs and suppression of colitis manifestations in mice. Biomed Pharmacother. 87:127–134.
  • Cheng J, Li W, Kang B, Zhou Y, Song J, Dan S, Yang Y, Zhang X, Li J, Yin S, et al. 2015. Tryptophan derivatives regulate the transcription of Oct4 in stem-like cancer cells. Nat Commun. 6:7209.
  • Chiaro CR, Patel RD, Marcus CB, Perdew GH. 2007. Evidence for an aryl hydrocarbon receptor-mediated cytochrome p450 autoregulatory pathway. Mol Pharmacol. 72:1369–1379.
  • Cho SW, Suzuki K, Miura Y, Miyazaki T, Nose M, Iwata H, Kim EY. 2015. Novel role of hnRNP-A2/B1 in modulating aryl hydrocarbon receptor ligand sensitivity. Arch Toxicol. 89:2027–2038.
  • Chung KT, Gadupudi GS. 2011. Possible roles of excess tryptophan metabolites in cancer. Environ Mol Mutagen. 52:81–104.
  • Cibrian D, Saiz ML, de la Fuente H, Sanchez-Diaz R, Moreno-Gonzalo O, Jorge I, Ferrarini A, Vazquez J, Punzon C, Fresno M, et al. 2016. CD69 controls the uptake of l-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis. Nat Immunol. 17:985–996.
  • Contador-Troca M, Alvarez-Barrientos A, Merino JM, Morales-Hernandez A, Rodriguez MI, Rey-Barroso J, Barrasa E, Cerezo-Guisado MI, Catalina-Fernandez I, Saenz-Santamaria J, et al. 2015. Dioxin receptor regulates aldehyde dehydrogenase to block melanoma tumorigenesis and metastasis. Mol Cancer. 14:148.
  • Conti HR, Gaffen SL. 2015. IL-17-mediated immunity to the opportunistic fungal pathogen Candida albicans. J Immunol. 195:780–788.
  • Crawford RB, Holsapple MP, Kaminski NE. 1997. Leukocyte activation induces aryl hydrocarbon receptor up-regulation, DNA binding, and increased Cyp1a1 expression in the absence of exogenous ligand. Mol Pharmacol. 52:921–927.
  • Dere E, Forgacs AL, Zacharewski TR, Burgoon LD. 2011. Genome-wide computational analysis of dioxin response element location and distribution in the human, mouse, and rat genomes. Chem Res Toxicol. 24:494–504.
  • Di Meglio P, Duarte JH, Ahlfors H, Owens ND, Li Y, Villanova F, Tosi I, Hirota K, Nestle FO, Mrowietz U, et al. 2014. Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions. Immunity. 40:989–1001.
  • Dorgham K, Amoura Z, Parizot C, Arnaud L, Frances C, Pionneau C, Devilliers H, Pinto S, Zoorob R, Miyara M, et al. 2015. Ultraviolet light converts propranolol, a nonselective β-blocker and potential lupus-inducing drug, into a proinflammatory AhR ligand. Eur J Immunol. 45:3174–3187.
  • Drozdzik A, Dziedziejko V, Kurzawski M. 2014. IL-1 and TNF-alpha regulation of aryl hydrocarbon receptor (AhR) expression in HSY human salivary cells. Arch Oral Biol. 59:434–439.
  • 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:e79819.
  • Effner R, Hiller J, Eyerich S, Traidl-Hoffmann C, Brockow K, Triggiani M, Behrendt H, Schmidt-Weber CB, Buters JT. 2017. Cytochrome P450s in human immune cells regulate IL-22 and c-Kit via an AHR feedback loop. Sci Rep. 7:44005.
  • Ehrlich AK, Pennington JM, Bisson WH, Kolluri SK, Kerkvliet NI. 2018. TCDD, FICZ, and other high affinity AhR ligands dose-dependently determine the fate of CD4+ T cell differentiation. Toxicol Sci. 161:310–320.
  • Ekins S, Reschly EJ, Hagey LR, Krasowski MD. 2008. Evolution of pharmacologic specificity in the pregnane X receptor. BMC Evol Biol. 8:103.
  • Esser C, Rannug A. 2015. The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol Rev. 67:259–279.
  • Esser C, Rannug A, Stockinger B. 2009. The aryl hydrocarbon receptor in immunity. Trends Immunol. 30:447–454.
  • Farmahin R, Crump D, Kennedy SW. 2014. Sensitivity of avian species to the aryl hydrocarbon receptor ligand 6-formylindolo [3,2-b] carbazole (FICZ). Chem Biol Interact. 221:61–69.
  • Farmahin R, Crump D, O'Brien JM, Jones SP, Kennedy SW. 2016. Time-dependent transcriptomic and biochemical responses of 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are explained by AHR activation time. Biochem Pharmacol. 115:134–143.
  • Faust D, Vondráček J, Krčmář P, Smerdová L, Procházková J, Hrubá E, Hulinková P, Kaina B, Dietrich C, Machala M. 2013. AhR-mediated changes in global gene expression in rat liver progenitor cells. Arch Toxicol. 87:681–698.
  • Fernandez-Salguero PM, Ward JM, Sundberg JP, Gonzalez FJ. 1997. Lesions of aryl-hydrocarbon receptor-deficient mice. Vet Pathol. 34:605–614.
  • Fritsche E, Schafer C, Calles C, Bernsmann T, Bernshausen T, Wurm M, Hubenthal U, Cline JE, Hajimiragha H, Schroeder P, et al. 2007. Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation. Proc Natl Acad Sci USA. 104:8851–8856.
  • Fu J, Nogueira SV, Drongelen VV, Coit P, Ling S, Rosloniec EF, Sawalha AH, Holoshitz J. 2018. Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environment interaction in autoimmune arthritis. Proc Natl Acad Sci USA. 115:4755–4760.
  • Gagliani N, Amezcua Vesely MC, Iseppon A, Brockmann L, Xu H, Palm NW, de Zoete MR, Licona-Limon P, Paiva RS, Ching T, et al. 2015. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature. 523:221–225.
  • Gandhi R, Kumar D, Burns EJ, Nadeau M, Dake B, Laroni A, Kozoriz D, Weiner HL, Quintana FJ. 2010. Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells. Nat Immunol. 11:846–853.
  • Gao J, Xu K, Liu H, Liu G, Bai M, Peng C, Li T, Yin Y. 2018. Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol. 8:13.
  • Garrett RW, Gasiewicz TA. 2006. The aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin alters the circadian rhythms, quiescence, and expression of clock genes in murine hematopoietic stem and progenitor cells. Mol Pharmacol. 69:2076–2083.
  • Gasiewicz TA, Singh KP, Bennett JA. 2014. The Ah receptor in stem cell cycling, regulation, and quiescence. Ann NY Acad Sci. 1310:44–50.
  • Gerbal-Chaloin S, Iankova I, Maurel P, Daujat-Chavanieu M. 2013. Nuclear receptors in the cross-talk of drug metabolism and inflammation. Drug Metab Rev. 45:122–144.
  • Gialitakis M, Tolaini M, Li Y, Pardo M, Yu L, Toribio A, Choudhary JS, Niakan K, Papayannopoulos V, Stockinger B. 2017. Activation of the aryl hydrocarbon receptor interferes with early embryonic development. Stem Cell Rep. 9:1377–1386.
  • Girer NG, Murray IA, Omiecinski CJ, Perdew GH. 2016. Hepatic aryl hydrocarbon receptor attenuates fibroblast growth factor 21 expression. J Biol Chem. 291:15378–15387.
  • Goerz G, Barnstorf W, Winnekendonk G, Bolsen K, Fritsch C, Kalka K, Tsambaos D. 1996. Influence of UVA and UVB irradiation on hepatic and cutaneous P450 isoenzymes. Arch Dermatol Res. 289:46–51.
  • Goerz G, Merk H, Bolsen K, Tsambaos D, Berger H. 1983. Influence of chronic UV-light exposure on hepatic and cutaneous monooxygenases. Experientia. 39:385–386.
  • Hahn ME, Karchner SI, Merson RR. 2017. Diversity as opportunity: insights from 600 million years of AHR evolution. Curr Opin Toxicol. 2:58–71.
  • Hahn ME, Karchner SI, Shapiro MA, Perera SA. 1997. Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family. Proc Natl Acad Sci USA. 94:13743–13748.
  • Hancks DC, Kazazian HH Jr. 2012. Active human retrotransposons: variation and disease. Curr Opin Genet Dev. 22:191–203.
  • Hankinson O, Andersen RD, Birren BW, Sander F, Negishi M, Nebert DW. 1985. Mutations affecting the regulation of transcription of the cytochrome P1-450 gene in the mouse Hepa-1 cell line. J Biol Chem. 260:1790–1795.
  • Harrill JA, Parks BB, Wauthier E, Rowlands JC, Reid LM, Thomas RS. 2015. Lineage-dependent effects of aryl hydrocarbon receptor agonists contribute to liver tumorigenesis. Hepatology. 61:548–560.
  • Hayes MD, Ovcinnikovs V, Smith AG, Kimber I, Dearman RJ. 2014. The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development. PLoS One. 9:e106955.
  • Henry EC, Welle SL, Gasiewicz TA. 2010. TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts. Toxicol Sci. 114:90–100.
  • Hirano M, Hwang JH, Park HJ, Bak SM, Iwata H, Kim EY. 2015. In silico analysis of the interaction of avian aryl hydrocarbon receptors and dioxins to decipher isoform-, ligand-, and species-specific activations. Environ Sci Technol. 49:3795–3804.
  • Hou Q, Ye L, Liu H, Huang L, Yang Q, Turner JR, Yu Q. 2018. Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22. Cell Death Differ. https://doi.org/10.1038/s41418-018-0070-2
  • Hu P, Herrmann R, Bednar A, Saloupis P, Dwyer MA, Yang P, Qi X, Thomas RS, Jaffe GJ, Boulton ME, et al. 2013. Aryl hydrocarbon receptor deficiency causes dysregulated cellular matrix metabolism and age-related macular degeneration-like pathology. Proc Natl Acad Sci USA. 110:E4069–E4078.
  • Huai W, Zhao R, Song H, Zhao J, Zhang L, Zhang L, Gao C, Han L, Zhao W. 2014. Aryl hydrocarbon receptor negatively regulates NLRP3 inflammasome activity by inhibiting NLRP3 transcription. Nat Commun. 5:4738.
  • Huang P, Ceccatelli S, Rannug A. 2002. A study on diurnal mRNA expression of CYP1A1, AHR, ARNT, and PER2 in rat pituitary and liver. Environ Toxicol Pharmacol. 11:119–126.
  • Ilchmann A, Krause M, Heilmann M, Burgdorf S, Vieths S, Toda M. 2012. Impact of culture medium on maturation of bone marrow-derived murine dendritic cells via the aryl hydrocarbon receptor. Mol Immunol. 51:42–50.
  • Ito S, Chen C, Satoh J, Yim S, Gonzalez FJ. 2007. Dietary phytochemicals regulate whole-body CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator-dependent system in gut. J Clin Invest. 117:1940–1950.
  • Ivanov II, Frutos RL, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, Finlay BB, Littman DR. 2008. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 4:337–349.
  • Jackson DP, Joshi AD, Elferink CJ. 2015. Ah receptor pathway intricacies; signaling through diverse protein partners and DNA-motifs. Toxicol Res (Camb). 4:1143–1158.
  • Janosik T, Rannug A, Rannug U, Wahlström N, Slätt J, Bergman J. 2018. The chemistry and properties of indolocarbazoles. Chem Rev. http://dx.doi.org/10.1021/acs.chemrev.8b00186.
  • 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. 13:377–385.
  • Ji T, Xu C, Sun L, Yu M, Peng K, Qiu Y, Xiao W, Yang H. 2015. Aryl hydrocarbon receptor activation down-regulates IL-7 and reduces inflammation in a mouse model of DSS-induced colitis. Dig Dis Sci. 60:1958–1966.
  • Jin UH, Lee SO, Sridharan G, Lee K, Davidson LA, Jayaraman A, Chapkin RS, Alaniz R, Safe S. 2014. Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor-dependent agonist and antagonist activities. Mol Pharmacol. 85:777–788.
  • John K, Lahoti TS, Wagner K, Hughes JM, Perdew GH. 2014. The Ah receptor regulates growth factor expression in head and neck squamous cell carcinoma cell lines. Mol Carcinogen. 53:765–776.
  • Jonsson ME, Franks DG, Woodin BR, Jenny MJ, Garrick RA, Behrendt L, Hahn ME, Stegeman JJ. 2009. The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) binds multiple AHRs and induces multiple CYP1 genes via AHR2 in zebrafish. Chem Biol Interact. 181:447–454.
  • Jonsson ME, Mattsson A, Shaik S, Brunstrom B. 2016. Toxicity and cytochrome P450 1A mRNA induction by 6-formylindolo[3,2-b]carbazole (FICZ) in chicken and Japanese quail embryos. Comp Biochem Physiol C Toxicol Pharmacol. 179:125–136.
  • Jurado-Manzano BB, Zavala-Reyes D, Turrubiartes-Martinez EA, Portales-Perez DP, Gonzalez-Amaro R, Layseca-Espinosa E. 2017. FICZ generates human tDCs that induce CD4+ CD25high Foxp3+ Treg-like cell differentiation. Immunol Lett. 190:84–92.
  • Jux B, Kadow S, Luecke S, Rannug A, Krutmann J, Esser C. 2011. The aryl hydrocarbon receptor mediates UVB radiation-induced skin tanning. J Investig Dermatol. 131:203–210.
  • Kado S, Chang WL, Chi AN, Wolny M, Shepherd DM, Vogel CF. 2017. Aryl hydrocarbon receptor signaling modifies Toll-like receptor-regulated responses in human dendritic cells. Arch Toxicol. 91:2209–2221.
  • Katiyar SK, Matsui MS, Mukhtar H. 2000. Ultraviolet-B exposure of human skin induces cytochromes P450 1A1 and 1B1. J Invest Dermatol. 114:328–333.
  • Kawajiri K, Kobayashi Y, Ohtake F, Ikuta T, Matsushima Y, Mimura J, Pettersson S, Pollenz RS, Sakaki T, Hirokawa T, et al. 2009. Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in ApcMin/+ mice with natural ligands. Proc Natl Acad Sci USA. 106:13481–13486.
  • Kawasaki H, Chang HW, Tseng HC, Hsu SC, Yang SJ, Hung CH, Zhou Y, Huang SK. 2014. A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor. Allergy. 69:445–452.
  • Ke S, Rabson AB, Germino JF, Gallo MA, Tian Y. 2001. Mechanism of suppression of cytochrome P-450 1A1 expression by tumor necrosis factor-alpha and lipopolysaccharide. J Biol Chem. 276:39638–39644.
  • Kim IS, Hwang JH, Hirano M, Iwata H, Kim EY. 2016. In vitro and in silico evaluation of transactivation potencies of avian AHR1 and AHR2 by endogenous ligands: implications for the physiological role of avian AHR2. Comp Biochem Physiol C Toxicol Pharmacol. 187:1–9.
  • Kim SY, Yang HJ, Chang YS, Kim JW, Brooks M, Chew EY, Wong WT, Fariss RN, Rachel RA, Cogliati T, et al. 2014. Deletion of aryl hydrocarbon receptor AHR in mice leads to subretinal accumulation of microglia and RPE atrophy. Invest Ophthalmol Vis Sci. 55:6031–6040.
  • Kimura A, Abe H, Tsuruta S, Chiba S, Fujii-Kuriyama Y, Sekiya T, Morita R, Yoshimura A. 2014. Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production. Int Immunol. 26:209–220.
  • Kimura A, Naka T, Nohara K, Fujii-Kuriyama Y, Kishimoto T. 2008. Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells. Proc Natl Acad Sci USA. 105:9721–9726.
  • 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. 334:1561–1565.
  • Kiyomatsu-Oda M, Uchi H, Morino-Koga S, Furue M. 2018. Protective role of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous ligand for arylhydrocarbon receptor, in chronic mite-induced dermatitis. J Dermatol Sci. 90:284–294.
  • Ko C-I, Puga A. 2017. Does the aryl hydrocarbon receptor regulate pluripotency? Curr Opin Toxicol. 2:1–7.
  • Ko CI, Fan Y, de Gannes M, Wang Q, Xia Y, Puga A. 2016. Repression of the aryl hydrocarbon receptor is required to maintain mitotic progression and prevent loss of pluripotency of embryonic stem cells. Stem Cells. 34:2825–2839.
  • Ko CI, Wang Q, Fan Y, Xia Y, Puga A. 2014. Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells. Stem Cell Res. 12:296–308.
  • 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 feedback mechanism in human Langerhans cells involving FcepsilonRI and IDO. Allergy. 72:1686–1693.
  • Lahvis GP, Lindell SL, Thomas RS, McCuskey RS, Murphy C, Glover E, Bentz M, Southard J, Bradfield CA. 2000. Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice. Proc Natl Acad Sci USA. 97:10442–10447.
  • Laiosa MD, Wyman A, Murante FG, Fiore NC, Staples JE, Gasiewicz TA, Silverstone AE. 2003. Cell proliferation arrest within intrathymic lymphocyte progenitor cells causes thymic atrophy mediated by the aryl hydrocarbon receptor. J Immunol. 171:4582–4591.
  • Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, et al. 2016. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 22:598–605.
  • Lanis JM, Alexeev EE, Curtis VF, Kitzenberg DA, Kao DJ, Battista KD, Gerich ME, Glover LE, Kominsky DJ, Colgan SP. 2017. Tryptophan metabolite activation of the aryl hydrocarbon receptor regulates IL-10 receptor expression on intestinal epithelia. Mucosal Immunol. 10:1133–1144.
  • Latchney SE, Lioy DT, Henry EC, Gasiewicz TA, Strathmann FG, Mayer-Proschel M, Opanashuk LA. 2011. Neural precursor cell proliferation is disrupted through activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Stem Cells Dev. 20:313–326.
  • Laub LB, Jones BD, Powell WH. 2010. Responsiveness of a Xenopus laevis cell line to the aryl hydrocarbon receptor ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chem Biol Interact. 183:202–211.
  • Lee JS, Cella M, McDonald KG, Garlanda C, Kennedy GD, Nukaya M, Mantovani A, Kopan R, Bradfield CA, Newberry RD, et al. 2011. AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat Immunol. 13:144–151.
  • Lee YH, Lin CH, Hsu PC, Sun YY, Huang YJ, Zhuo JH, Wang CY, Gan YL, Hung CC, Kuan CY, et al. 2015. Aryl hydrocarbon receptor mediates both proinflammatory and anti-inflammatory effects in lipopolysaccharide-activated microglia. Glia. 63:1138–1154.
  • Lensu S, Tuomisto JT, Tuomisto J, Pohjanvirta R. 2011. Characterization of the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-provoked strong and rapid aversion to unfamiliar foodstuffs in rats. Toxicology. 283:140–150.
  • Leung A, Zulick E, Skvir N, Vanuytsel K, Morrison TA, Naing ZH, Wang Z, Dai Y, Chui DHK, Steinberg MH, et al. 2018. Notch and aryl hydrocarbon receptor signaling impact definitive hematopoiesis from human pluripotent stem cells. Stem Cells. 36:1004–1019.
  • 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. 147:629–640.
  • Luecke S, Backlund M, Jux B, Esser C, Krutmann J, Rannug A. 2010. The aryl hydrocarbon receptor (AHR), a novel regulator of human melanogenesis. Pigm Cell Melanoma Res. 23:828–833.
  • Luecke S, Wincent E, Backlund M, Rannug U, Rannug A. 2010. Cytochrome P450 1A1 gene regulation by UVB involves crosstalk between the aryl hydrocarbon receptor and nuclear factor kappaB. Chem Biol Interact. 184:466–473.
  • Maaetoft-Udsen K, Shimoda LMN, Frøkiaer H, Turner H. 2012. Aryl hydrocarbon receptor ligand effects in RBL2H3 cells. J Immunotoxicol. 9:327–337.
  • Magiatis P, Pappas P, Gaitanis G, Mexia N, Melliou E, Galanou M, Vlachos C, Stathopoulou K, Skaltsounis AL, Marselos M, et al. 2013. Malassezia yeasts produce a collection of exceptionally potent activators of the Ah (dioxin) receptor detected in diseased human skin. J Invest Dermatol. 133:2023–2030.
  • Mahiout S, Pohjanvirta R. 2016. Aryl hydrocarbon receptor agonists trigger avoidance of novel food in rats. Physiol Behav. 167:49–59.
  • Marcus RS, Holsapple MP, Kaminski NE. 1998. Lipopolysaccharide activation of murine splenocytes and splenic B cells increased the expression of aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator. J Pharmacol Exp Ther. 287:1113–1118.
  • Martin B, Hirota K, Cua DJ, Stockinger B, Veldhoen M. 2009. Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity. 31:321–330.
  • McIntosh BE, Hogenesch JB, Bradfield CA. 2010. Mammalian Per-Arnt-Sim proteins in environmental adaptation. Annu Rev Physiol. 72:625–645.
  • Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. 2010. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol. 185:3190–3198.
  • Mezrich JD, Nguyen LP, Kennedy G, Nukaya M, Fechner JH, Zhang X, Xing Y, Bradfield CA. 2012. SU5416, a VEGF receptor inhibitor and ligand of the AHR, represents a new alternative for immunomodulation. PLoS One. 7:e44547.
  • Mitchell KA, Elferink CJ. 2009. Timing is everything: consequences of transient and sustained AhR activity. Biochem Pharmacol. 77:947–956.
  • Miyagi S, Murata K, Sashino K, Sawamura S, Uruno S, Yoshimura S, Akahoshi E, Ishihara-Sugano M, Itoh S, Kurita N. 2015. Binding affinity between AhR and exogenous/endogenous ligands: molecular simulations and biological experiment. Mol Simul. 41:555–563.
  • Mohammadi-Bardbori A, Akbarizadeh AR, Delju F, Rannug A. 2016. Chromatin remodeling by curcumin alters endogenous aryl hydrocarbon receptor signaling. Chem Biol Interact. 252:19–27.
  • Mohammadi-Bardbori A, Bastan F, Akbarizadeh AR. 2017. The highly bioactive molecule and signal substance 6-formylindolo[3,2-b]carbazole (FICZ) plays bi-functional roles in cell growth and apoptosis in vitro. Arch Toxicol. 91:3365–3372.
  • Mohammadi-Bardbori A, Vikstrom Bergander L, Rannug U, Rannug A. 2015. NADPH oxidase-dependent mechanism explains how arsenic and other oxidants can activate aryl hydrocarbon receptor signaling. Chem Res Toxicol. 28:2278–2286.
  • Mohinta S, Kannan AK, Gowda K, Amin SG, Perdew GH, August A. 2015. Differential regulation of Th17 and T regulatory cell differentiation by aryl hydrocarbon receptor dependent xenobiotic response element dependent and independent pathways. Toxicol Sci. 145:233–243.
  • Monteleone I, Marafini I, Zorzi F, Di Fusco D, Dinallo V, Rizzo A, Sileri P, Sica G, Monteleone G. 2016. Smad7 Knockdown Restores Aryl Hydrocarbon Receptor-mediated Protective Signals in the Gut. J Crohns Colitis. 10:670–677.
  • Monteleone I, Rizzo A, Sarra M, Sica G, Sileri P, Biancone L, MacDonald TT, Pallone F, Monteleone G. 2011. Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract. Gastroenterology. 141:237–248.
  • Monteleone I, Zorzi F, Marafini I, Di Fusco D, Dinallo V, Caruso R, Izzo R, Franze E, Colantoni A, Pallone F, et al. 2016. Aryl hydrocarbon receptor-driven signals inhibit collagen synthesis in the gut. Eur J Immunol. 46:1047–1057.
  • Morales-Hernández A, González-Rico FJ, Román AC, Rico-Leo E, Alvarez-Barrientos A, Sánchez L, Macia Á, Heras SR, García-Pérez JL, Merino JM, et al. 2016. Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor. Nucleic Acids Res. 44:4665–4683.
  • Morales-Hernandez A, Nacarino-Palma A, Moreno-Marin N, Barrasa E, Paniagua-Quinones B, Catalina-Fernandez I, Alvarez-Barrientos A, Bustelo XR, Merino JM, Fernandez-Salguero PM. 2017. Lung regeneration after toxic injury is improved in absence of dioxin receptor. Stem Cell Res. 25:61–71.
  • Moran TB, Brannick KE, Raetzman LT. 2012. Aryl-hydrocarbon receptor activity modulates prolactin expression in the pituitary. Toxicol Appl Pharmacol. 265:139–145.
  • Morino-Koga S, Uchi H, Mitoma C, Wu Z, Kiyomatsu M, Fuyuno Y, Nagae K, Yasumatsu M, Suico MA, Kai H, et al. 2017. 6-Formylindolo[3,2-b]carbazole accelerates skin wound healing via activation of ERK, but not aryl hydrocarbon receptor. J Invest Dermatol. 137:2217–2226.
  • Morino-Koga S, Uchi H, Tsuji G, Takahara M, Kajiwara J, Hirata T, Furue M. 2013. Reduction of CC-chemokine ligand 5 by aryl hydrocarbon receptor ligands. J Dermatol Sci. 72:9–15.
  • Moura-Alves P, Fae K, Houthuys E, Dorhoi A, Kreuchwig A, Furkert J, Barison N, Diehl A, Munder A, Constant P, et al. 2014. AhR sensing of bacterial pigments regulates antibacterial defence. Nature. 512:387–392.
  • Mukai M, Lin TM, Peterson RE, Cooke PS, Tischkau SA. 2008. Behavioral rhythmicity of mice lacking AhR and attenuation of light-induced phase shift by 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Rhythms. 23:200–210.
  • Mukai M, Tischkau SA. 2007. Effects of tryptophan photoproducts in the circadian timing system: searching for a physiological role for aryl hydrocarbon receptor. Toxicol Sci. 95:172–181.
  • Murai M, Tsuji G, Hashimoto-Hachiya A, Kawakami Y, Furue M, Mitoma C. 2018. An endogenous tryptophan photo-product, FICZ, is potentially involved in photo-aging by reducing TGF-beta-regulated collagen homeostasis. J Dermatol Sci. 89:19–26.
  • Murray IA, Patterson AD, Perdew GH. 2014. Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nat Rev Cancer. 14:801–814.
  • Murray IA, Perdew GH. 2017. Ligand activation of the Ah receptor contributes to gastrointestinal homeostasis. Curr Opin Toxicol. 2:15–23.
  • Nakahama T, Hanieh H, Nguyen NT, Chinen I, Ripley B, Millrine D, Lee S, Nyati KK, Dubey PK, Chowdhury K, et al. 2013. Aryl hydrocarbon receptor-mediated induction of the microRNA-132/212 cluster promotes interleukin-17-producing T-helper cell differentiation. Proc Natl Acad Sci USA. 110:11964–11969.
  • Nebert DW. 1991. Proposed role of drug-metabolizing enzymes: regulation of steady state levels of the ligands that effect growth, homeostasis, differentiation, and neuroendocrine functions. Mol Endocrinol. 5:1203–1214.
  • Nebert DW, Brown DD, Towne DW, Eisen HJ. 1984. Association of fertility, fitness and longevity with the murine Ah locus among (C57BL/6N) (C3H/HeN) recombinant inbred lines. Biol Reprod. 30:363–373.
  • Nebert DW, Dalton TP. 2006. The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer. 6:947–960.
  • Nguyen CH, Brenner S, Huttary N, Atanasov AG, Dirsch VM, Chatuphonprasert W, Holzner S, Stadler S, Riha J, Krieger S, et al. 2016. AHR/CYP1A1 interplay triggers lymphatic barrier breaching in breast cancer spheroids by inducing 12(S)-HETE synthesis. Hum Mol Genet. 25:5006–5016.
  • Novikov O, Wang Z, Stanford EA, Parks AJ, Ramirez-Cardenas A, Landesman E, Laklouk I, Sarita-Reyes C, Gusenleitner D, Li A, et al. 2016. An aryl hydrocarbon receptor-mediated amplification loop that enforces cell migration in ER-/PR-/Her2-human breast cancer cells. Mol Pharmacol. 90:674–688.
  • 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. 54:3373–3383.
  • Oberg M, Bergander L, Hakansson H, Rannug U, Rannug A. 2005. Identification of the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole, in cell culture medium, as a factor that controls the background aryl hydrocarbon receptor activity. Toxicol Sci. 85:935–943.
  • Okamoto T, Mitsuhashi M, Fujita I, Sindhu RK, Kikkawa Y. 1993. Induction of cytochrome P450 1A1 and 1A2 by hyperoxia. Biochem Biophys Res Commun. 197:878–885.
  • Okudaira N, Iijima K, Koyama T, Minemoto Y, Kano S, Mimori A, Ishizaka Y. 2010. Induction of long interspersed nucleotide element-1 (L1) retrotransposition by 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct. Proc Natl Acad Sci USA. 107:18487–18492.
  • Park JH, Choi AJ, Kim SJ, Cheong SW, Jeong SY. 2016. AhR activation by 6-formylindolo[3,2-b]carbazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibit the development of mouse intestinal epithelial cells. Environ Toxicol Pharmacol. 43:44–53.
  • Park SL, Justiniano R, Williams JD, Cabello CM, Qiao S, Wondrak GT. 2015. The tryptophan-derived endogenous aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole is a nanomolar UVA photosensitizer in epidermal keratinocytes. J Invest Dermatol. 135:1649–1658.
  • Pauly SK, Fechner JH, Zhang X, Torrealba J, Bradfield CA, Mezrich JD. 2012. The aryl hydrocarbon receptor influences transplant outcomes in response to environmental signals. Toxicol Environ Chem. 94:1175–1187.
  • Perdew GH, Babbs CF. 1991. Production of Ah receptor ligands in rat fecal suspensions containing tryptophan or indole-3-carbinol. Nutr Cancer. 16:209–218.
  • Peres AG, Zamboni R, King IL, Madrenas J. 2017. Suppression of CYP1 members of the AHR response by pathogen-associated molecular patterns. J Leukoc Biol. 102:1471–1480.
  • Petrulis JR, Perdew GH. 2002. The role of chaperone proteins in the aryl hydrocarbon receptor core complex. Chem Biol Interact. 141:25–40.
  • Pilz C, Feyerabend T, Sonner J, Redaelli C, Peter K, Kunze A, Haas K, Esser C, Schakel K, Wick W, et al. 2016. Normal mast cell numbers in the tissues of AhR-deficient mice. Exp Dermatol. 25:62–63.
  • Poland A, Glover E, Kende AS. 1976. Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. J Biol Chem. 251:4936–4946.
  • Poland A, Knutson JC. 1982. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annu Rev Pharmacol Toxicol. 22:517–554.
  • Prochazkova J, Strapacova S, Svrzkova L, Andrysik Z, Hyzdalova M, Hruba E, Pencikova K, Libalova H, Topinka J, Klema J, et al. 2018. Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 292:162–174.
  • Prud'homme GJ, Glinka Y, Toulina A, Ace O, Subramaniam V, Jothy S. 2010. Breast cancer stem-like cells are inhibited by a non-toxic aryl hydrocarbon receptor agonist. PLoS One. 5:e13831.
  • Qiu J, Heller JJ, Guo X, Chen ZM, Fish K, Fu YX, Zhou L. 2012. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity. 36:92–104.
  • 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. 453:65–71.
  • Ramirez JM, Brembilla NC, Sorg O, Chicheportiche R, Matthes T, Dayer JM, Saurat JH, Roosnek E, Chizzolini C. 2010. Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells. Eur J Immunol. 40:2450–2459.
  • Rannug A, Rannug U, Rosenkranz HS, Winqvist L, Westerholm R, Agurell E, Grafstrom AK. 1987. Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J Biol Chem. 262:15422–15427.
  • Rannug U, Agurell E, Rannug A, Cederberg H. 1992. Certain tryptophan photoproducts are inhibitors of cytochrome P450-dependent mutagenicity. Environ Mol Mutagen. 20:289–296.
  • Rannug U, Bramstedt H, Nilsson U. 1992. The presence of genotoxic and bioactive components in indigo dyed fabrics-a possible health risk? Mutat Res. 282:219–225.
  • Rannug U, Rannug A, Sjoberg U, Li H, Westerholm R, Bergman J. 1995. Structure elucidation of two tryptophan-derived, high affinity Ah receptor ligands. Chem Biol. 2:841–845.
  • Rentas S, Holzapfel N, Belew MS, Pratt G, Voisin V, Wilhelm BT, Bader GD, Yeo GW, Hope KJ. 2016. Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells. Nature. 532:508–511.
  • Reschly EJ, Ai N, Welsh WJ, Ekins S, Hagey LR, Krasowski MD. 2008. Ligand specificity and evolution of liver X receptors. J Steroid Biochem Mol Biol. 110:83–94.
  • Reschly EJ, Bainy AC, Mattos JJ, Hagey LR, Bahary N, Mada SR, Ou J, Venkataramanan R, Krasowski MD. 2007. Functional evolution of the vitamin D and pregnane X receptors. BMC Evol Biol. 7:222.
  • Rico-Leo EM, Alvarez-Barrientos A, Fernandez-Salguero PM. 2013. Dioxin receptor expression inhibits basal and transforming growth factor β-induced epithelial-to-mesenchymal transition. J Biol Chem. 288:7841–7856.
  • Rico-Leo EM, Moreno-Marin N, Gonzalez-Rico FJ, Barrasa E, Ortega-Ferrusola C, Martin-Munoz P, Sanchez-Guardado LO, Llano E, Alvarez-Barrientos A, Infante-Campos A, et al. 2016. piRNA-associated proteins and retrotransposons are differentially expressed in murine testis and ovary of aryl hydrocarbon receptor deficient mice. Open Biol. 6:160186.
  • Roblin S, Okey AB, Harper PA. 2004. AH receptor antagonist inhibits constitutive CYP1A1 and CYP1B1 expression in rat BP8 cells. Biochem Biophys Res Commun. 317:142–148.
  • Romanov S, Medvedev A, Gambarian M, Poltoratskaya N, Moeser M, Medvedeva L, Gambarian M, Diatchenko L, Makarov S. 2008. Homogeneous reporter system enables quantitative functional assessment of multiple transcription factors. Nat Methods. 5:253–260.
  • Rutz S, Noubade R, Eidenschenk C, Ota N, Zeng W, Zheng Y, Hackney J, Ding J, Singh H, Ouyang W. 2011. Transcription factor c-Maf mediates the TGF-beta-dependent suppression of IL-22 production in T(H)17 cells. Nat Immunol. 12:1238–1245.
  • Safe S, Lee SO, Jin UH. 2013. Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target. Toxicol Sci. 135:1–16.
  • Salisbury TB, Tomblin JK, Primerano DA, Boskovic G, Fan J, Mehmi I, Fletcher J, Santanam N, Hurn E, Morris GZ, Denvir J. 2014. Endogenous aryl hydrocarbon receptor promotes basal and inducible expression of tumor necrosis factor target genes in MCF-7 cancer cells. Biochem Pharmacol. 91:390–399.
  • Sartor MA, Schnekenburger M, Marlowe JL, Reichard JF, Wang Y, Fan Y, Ma C, Karyala S, Halbleib D, Liu X, et al. 2009. Genomewide analysis of aryl hydrocarbon receptor binding targets reveals an extensive array of gene clusters that control morphogenetic and developmental programs. Environ Health Perspect. 117:1139–1146.
  • Sauzeau V, Carvajal-Gonzalez JM, Riolobos AS, Sevilla MA, Menacho-Marquez M, Roman AC, Abad A, Montero MJ, Fernandez-Salguero P, Bustelo XR. 2011. Transcriptional factor aryl hydrocarbon receptor (Ahr) controls cardiovascular and respiratory functions by regulating the expression of the Vav3 proto-oncogene. J Biol Chem. 286:2896–2909.
  • Schaldach CM, Riby J, Bjeldanes LF. 1999. Lipoxin A4: a new class of ligand for the Ah receptor. Biochemistry. 38:7594–7600.
  • Schallreuter KU, Salem MA, Gibbons NC, Maitland DJ, Marsch E, Elwary SM, Healey AR. 2012. Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 2: Epidermal H2O2/ONOO(-)-mediated stress in vitiligo hampers indoleamine 2,3-dioxygenase and aryl hydrocarbon receptor-mediated immune response signaling. FASEB J. 26:2471?2485.
  • Schiering C, Vonk A, Das S, Stockinger B, Wincent E. 2018. Cytochrome P4501-inhibiting chemicals amplify aryl hydrocarbon receptor activation and IL-22 production in T helper 17 cells. Biochem Pharmacol. 151:47–58.
  • Schiering C, Wincent E, Metidji A, Iseppon A, Li Y, Potocnik AJ, Omenetti S, Henderson CJ, Wolf CR, Nebert DW, et al. 2017. Feedback control of AHR signalling regulates intestinal immunity. Nature. 542:242–245.
  • Schmidt JV, Su GH, Reddy JK, Simon MC, Bradfield CA. 1996. Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development. Proc Natl Acad Sci USA. 93:6731–6736.
  • Schulte KW, Green E, Wilz A, Platten M, Daumke O. 2017. Structural basis for aryl hydrocarbon receptor-mediated gene activation. Structure. 25:1025–1033 e3.
  • Schulz VJ, Smit JJ, Huijgen V, Bol-Schoenmakers M, van Roest M, Kruijssen LJ, Fiechter D, Hassing I, Bleumink R, Safe S, et al. 2012. Non-dioxin-like AhR ligands in a mouse peanut allergy model. Toxicol Sci. 128:92–102.
  • Sekine H, Mimura J, Oshima M, Okawa H, Kanno J, Igarashi K, Gonzalez FJ, Ikuta T, Kawajiri K, Fujii-Kuriyama Y. 2009. Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock. Mol Cell Biol. 29:6391–6400.
  • Seok SH, Lee W, Jiang L, Molugu K, Zheng A, Li Y, Park S, Bradfield CA, Xing Y. 2017. Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex. Proc Natl Acad Sci USA. 114:5431–5436.
  • Seok SH, Ma ZX, Feltenberger JB, Chen H, Chen H, Scarlett C, Lin Z, Satyshur KA, Cortopassi M, Jefcoate CR, et al. 2018. Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR). J Biol Chem. 293:1994–2005.
  • Shimada T, Guengerich FP. 2006. Inhibition of human cytochrome P450 1A1-, 1A2-, and 1B1-mediated activation of procarcinogens to genotoxic metabolites by polycyclic aromatic hydrocarbons. Chem Res Toxicol. 19:288–294.
  • Shin JH, Zhang L, Murillo-Sauca O, Kim J, Kohrt HE, Bui JD, Sunwoo JB. 2013. Modulation of natural killer cell antitumor activity by the aryl hydrocarbon receptor. Proc Natl Acad Sci USA. 110:12391–12396.
  • 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. 189:120–127.
  • Simones T, Shepherd DM. 2011. Consequences of AhR activation in steady-state dendritic cells. Toxicol Sci. 119:293–307.
  • Singh KP, Casado FL, Opanashuk LA, Gasiewicz TA. 2009. The aryl hydrocarbon receptor has a normal function in the regulation of hematopoietic and other stem/progenitor cell populations. Biochem Pharmacol. 77:577–587.
  • Singh NP, Singh UP, Rouse M, Zhang J, Chatterjee S, Nagarkatti PS, Nagarkatti M. 2016. Dietary indoles suppress delayed-type hypersensitivity by inducing a switch from proinflammatory Th17 cells to anti-inflammatory regulatory T cells through regulation of microRNA. J Immunol. 196:1108–1122.
  • Singh NP, Singh UP, Singh B, Price RL, Nagarkatti M, Nagarkatti PS. 2011. Activation of aryl hydrocarbon receptor (AhR) leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis. PLoS One. 6:e23522.
  • Smirnova A, Wincent E, Vikstrom Bergander L, Alsberg T, Bergman J, Rannug A, Rannug U. 2016. Evidence for new light-independent pathways for generation of the endogenous aryl hydrocarbon receptor agonist FICZ. Chem Res Toxicol. 29:75–86.
  • Smith BW, Rozelle SS, Leung A, Ubellacker J, Parks A, Nah SK, French D, Gadue P, Monti S, Chui DH, et al. 2013. The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation. Blood. 122:376–385.
  • Smith KJ, Boyer JA, Muku GE, Murray IA, Gowda K, Desai D, Amin SG, Glick AB, Perdew GH. 2017. Editor's highlight: Ah receptor activation potentiates neutrophil chemoattractant (C-X-C Motif) ligand 5 expression in keratinocytes and skin. Toxicol Sci. 160:83–94.
  • Smith KJ, Murray IA, Boyer JA, Perdew GH. 2018. Allelic variants of the aryl hydrocarbon receptor differentially influence UVB-mediated skin inflammatory responses in SKH1 mice. Toxicology. 394:27–34.
  • Smith SH, Jayawickreme C, Rickard DJ, Nicodeme E, Bui T, Simmons C, Coquery CM, Neil J, Pryor WM, Mayhew D, et al. 2017. Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans. J Invest Dermatol. 137:2110–2119.
  • 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. 99:14694–14699.
  • Sonnenberg GF, Fouser LA, Artis D. 2011. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol. 12:383–390.
  • Stanford EA, Ramirez-Cardenas A, Wang Z, Novikov O, Alamoud K, Koutrakis P, Mizgerd JP, Genco CA, Kukuruzinska M, Monti S, et al. 2016. Role for the aryl hydrocarbon receptor and diverse ligands in oral squamous cell carcinoma migration and tumorigenesis. Mol Cancer Res. 14:696–706.
  • Stanford EA, Wang Z, Novikov O, Mulas F, Landesman-Bollag E, Monti S, Smith BW, Seldin DC, Murphy GJ, Sherr DH. 2016. The role of the aryl hydrocarbon receptor in the development of cells with the molecular and functional characteristics of cancer stem-like cells. BMC Biol. 14:20.
  • Stockinger B, Omenetti S. 2017. The dichotomous nature of T helper 17 cells. Nat Rev Immunol. 17:535–544.
  • Thatcher TH, Maggirwar SB, Baglole CJ, Lakatos HF, Gasiewicz TA, Phipps RP, Sime PJ. 2007. Aryl hydrocarbon receptor-deficient mice develop heightened inflammatory responses to cigarette smoke and endotoxin associated with rapid loss of the nuclear factor-kappaB component RelB. Am J Pathol. 170:855–864.
  • 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. 147:41–54.
  • Tijet N, Boutros PC, Moffat ID, Okey AB, Tuomisto J, Pohjanvirta R. 2006. Aryl hydrocarbon receptor regulates distinct dioxin-dependent and dioxin-independent gene batteries. Mol Pharmacol. 69:140–153.
  • Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H. 2009. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol. 10:864–871.
  • Tsuji G, Hashimoto-Hachiya A, Kiyomatsu-Oda M, Takemura M, Ohno F, Ito T, Morino-Koga S, Mitoma C, Nakahara T, Uchi H, et al. 2017. Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis. Cell Death Dis. 8:e2931.
  • Unnisa Z, Singh KP, Henry EC, Donegan CL, Bennett JA, Gasiewicz TA. 2016. Aryl hydrocarbon receptor deficiency in an Exon 3 deletion mouse model promotes hematopoietic stem cell proliferation and impacts endosteal niche cells. Stem Cells Int. 2016:4536187.
  • Veiga-Parga T, Suryawanshi A, Rouse BT. 2011. Controlling viral immuno-inflammatory lesions by modulating aryl hydrocarbon receptor signaling. PLoS Pathog. 7:e1002427.
  • Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, Stockinger B. 2008. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature. 453:106–109.
  • Villa M, Gialitakis M, Tolaini M, Ahlfors H, Henderson CJ, Wolf CR, Brink R, Stockinger B. 2017. Aryl hydrocarbon receptor is required for optimal B-cell proliferation. EMBO J. 36:116–128.
  • 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. 375:331–335.
  • Wang HC, Zhou Y, Huang SK. 2017. SHP-2 phosphatase controls aryl hydrocarbon receptor-mediated ER stress response in mast cells. Arch Toxicol. 91:1739–1748.
  • Wang Q, Yang K, Han B, Sheng B, Yin J, Pu A, Li L, Sun L, Yu M, Qiu Y, et al. 2018. Aryl hydrocarbon receptor inhibits inflammation in DSS induced colitis via the MK2/pMK2/TTP pathway. Int J Mol Med. 41:868–876.
  • Wang Y, Fan Y, Puga A. 2010. Dioxin exposure disrupts the differentiation of mouse embryonic stem cells into cardiomyocytes. Toxicol Sci. 115:225–237.
  • Wang Z, Monti S, Sherr DH. 2017. The diverse and important contributions of the AHR to cancer and cancer immunity. Curr Opin Toxicol. 2:93–102.
  • Wei YD, Bergander L, Rannug U, Rannug A. 2000. Regulation of CYP1A1 transcription via the metabolism of the tryptophan-derived 6-formylindolo[3,2-b]carbazole. Arch Biochem Biophys. 383:99–107.
  • Wei YD, Helleberg H, Rannug U, Rannug A. 1998. Rapid and transient induction of CYP1A1 gene expression in human cells by the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole. Chem Biol Interact. 110:39–55.
  • Wei YD, Rannug U, Rannug A. 1999. UV-induced CYP1A1 gene expression in human cells is mediated by tryptophan. Chem Biol Interact. 118:127–140.
  • Weiss C, Kolluri SK, Kiefer F, Gottlicher M. 1996. Complementation of Ah receptor deficiency in hepatoma cells. Negative feedback regulation and cell cycle control by the Ah receptor. Exp Cell Res. 226:154–163.
  • Wheeler JL, Martin KC, Resseguie E, Lawrence BP. 2014. Differential consequences of two distinct AhR ligands on innate and adaptive immune responses to influenza A virus. Toxicol Sci. 137:324–334.
  • Wincent E, Amini N, Luecke S, Glatt H, Bergman J, Crescenzi C, Rannug A, Rannug U. 2009. The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans. J Biol Chem. 284:2690–2696.
  • Wincent E, Bengtsson J, Mohammadi Bardbori A, Alsberg T, Luecke S, Rannug U, Rannug A. 2012. Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ as a mechanism for activation of the aryl hydrocarbon receptor. Proc Natl Acad Sci USA. 109:4479–4484.
  • Wincent E, Kubota A, Timme-Laragy A, Jonsson ME, Hahn ME, Stegeman JJ. 2016. Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner. Biochem Pharmacol. 110–111:117–129.
  • Wincent E, Stegeman JJ, Jonsson ME. 2015. Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: implications for physiological and toxicological AHR functions. Toxicol Appl Pharmacol. 284:163–179.
  • Woeller CF, Roztocil E, Hammond CL, Feldon SE, Phipps RP. 2016. the aryl hydrocarbon receptor and its ligands inhibit myofibroblast formation and activation: implications for thyroid eye disease. Am J Pathol. 186:3189–3202.
  • 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. 136:441–453.
  • Xu CX, Krager SL, Liao DF, Tischkau SA. 2010. Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene. Toxicol Sci. 115:98–108.
  • Yamada T, Horimoto H, Kameyama T, Hayakawa S, Yamato H, Dazai M, Takada A, Kida H, Bott D, Zhou AC, et al. 2016. Constitutive aryl hydrocarbon receptor signaling constrains type I interferon-mediated antiviral innate defense. Nat Immunol. 17:687–694.
  • Ye J, Qiu J, Bostick JW, Ueda A, Schjerven H, Li S, Jobin C, Chen ZE, Zhou L. 2017. The Aryl hydrocarbon receptor preferentially marks and promotes gut regulatory T cells. Cell Rep. 21:2277–2290.
  • Yin A, Korzh S, Winata CL, Korzh V, Gong Z. 2011. Wnt signaling is required for early development of zebrafish swimbladder. PLoS One. 6:e18431.
  • Yin J, Sheng B, Han B, Pu A, Yang K, Li P, Wang Q, Xiao W, Yang H. 2016. The AhR is involved in the regulation of LoVo cell proliferation through cell cycle-associated proteins. Cell Biol Int. 40:560–568.
  • Yoshioka W, Peterson RE, Tohyama C. 2011. Molecular targets that link dioxin exposure to toxicity phenotypes. J Steroid Biochem Mol Biol. 127:96–101.
  • Yu M, Wang Q, Ma Y, Li L, Yu K, Zhang Z, Chen G, Li X, Xiao W, Xu P, Yang H. 2018. Aryl hydrocarbon receptor activation modulates intestinal epithelial barrier function by maintaining tight junction integrity. Int J Biol Sci. 14:69–77.
  • Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, Zecchi R, D’Angelo C, Massi-Benedetti C, Fallarino F, et al. 2013. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 39:372–385.
  • Zhou Y, Tung HY, Tsai YM, Hsu SC, Chang HW, Kawasaki H, Tseng HC, Plunkett B, Gao P, Hung CH, et al. 2013. Aryl hydrocarbon receptor controls murine mast cell homeostasis. Blood. 121:3195–3204.