Kynurenine 3-monooxygenase mediates inhibition of Th17 differentiation via catabolism of endogenous aryl hydrocarbon receptor ligands

European Journal of Immunology

Volumn 43, Issue 7, 2013, Pages 1727-1734

  Stephens, Geoffrey L ^a   Wang, Qun ^a   Swerdlow, Bonnie ^a   Bhat, Geetha ^a   Kolbeck, Roland ^a   Fung, Michael ^a  

^a MEDIMMUNE   (United States)

Author keywords

Autoimmunity; Cell differentiation; T cells

Indexed keywords

AROMATIC HYDROCARBON RECEPTOR; GAMMA INTERFERON; KYNURENINE 3 MONOOXYGENASE; SMALL INTERFERING RNA;

ANIMAL CELL; ARTICLE; AUTOIMMUNITY; CATABOLISM; CELL DIFFERENTIATION; CONTROLLED STUDY; ENZYME INHIBITION; GASTRITIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TH1 CELL; TH17 CELL; TRYPTOPHAN METABOLISM;

AUTOIMMUNITY; CELL DIFFERENTIATION; T CELLS;

ANIMALS; BLOTTING, WESTERN; CELL DIFFERENTIATION; ENZYME INHIBITORS; FLOW CYTOMETRY; GENE KNOCKDOWN TECHNIQUES; INTERLEUKIN-17; KYNURENINE; KYNURENINE 3-MONOOXYGENASE; LIGANDS; METABOLISM; MICE; MICE, INBRED BALB C; RECEPTORS, ARYL HYDROCARBON; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; TH17 CELLS; TRYPTOPHAN;

EID: 84880016607     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201242779     Document Type: Article

References (24)

1. Hu, Y., Shen, F., Crellin, N. K. and Ouyang, W., The IL-17 pathway as a major therapeutic target in autoimmune diseases. Ann. N. Y. Acad. Sci. 2011. 1217: 60-76.
2. Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L. et al., Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006. 441: 235-238.
3. Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D. et al., Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006. 441: 231-234.
4. Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M. and Stockinger, B., TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006. 24: 179-189.
5. Schracksnadel, K., Wirleitner, B., Winkler, C. and Fuchs, D., Monitoring tryptophan metabolism in chronic immune activation. Clin. Chim. Acta 2006. 364: 82-90.
6. Opitz, C., Wick, W., Steinman, L. and Platten, M., Tryptophan degradation in autoimmune diseases. Cell. Mol. Life Sci. 2007. 64: 2542-2563.
7. Stone, T. W. and Darlington, L. G., Endogenous kynurenines as targets for drug discovery and development. Nat. Rev. Drug Discov. 2002. 1: 609-620.
8. Terness, P., Bauer, T. M., Röse, L., Dufter, C., Watzlik, A., Simon, H. and Opelz, G., Inhibition of allogeneic T cell proliferation by indoleamine 2, 3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J. Exp. Med. 2002. 196: 447-457.
9. Frumento, G., Rotondo, R., Tonetti, M., Damonte, G., Benatti, U. and Ferrara, G. B., Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2, 3-dioxygenase. J. Exp. Med. 2002. 196: 459-468.
10. Grohmann, U., Fallarino, F., Bianchi, R., Orabona, C., Vacca, C., Fioretti, M. C. and Puccetti, P., A defect in tryptophan catabolism impairs tolerance in nonobese diabetic mice. J. Exp. Med. 2003. 198: 153-160.
11. Veldhoen, M., Hirota, K., Christensen, J., O'Garra, A. and Stockinger, B., Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J. Exp. Med. 2009. 206: 43-49.
12. DiNatale, B. C., Murray, I. A., Schroeder, J. C., Flaveny, C. A., Lahoti, T. S., Laurenzana, E. M., Omiecinski, C. J. et al., Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol. Sci. 2010. 115: 89-97.
13. McMillan, B. J. and Bradfield, C. A., The aryl hydrocarbon receptor sans xenobiotics: endogenous function in genetic model systems. Mol. Pharmacol. 2007. 72: 487-498.
14. Mezrich, J. D., Fechner, J. H., Zhang, X., Johnson, B. P., Burlingham, W. J. and Bradfield, C. A., An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J. Immunol. 2010. 185: 3190-3198.
15. Nguyen, N. T., Kimura, A., Nakahama, T., Chinen, I., Masuda, K., Nohara, K., Fujii-Kuriyama, Y. et al., Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc. Natl. Acad. Sci. 2010. 107: 19961-19966.
16. Fernandez-Salguero, P., Pineau, T., Hilbert, D. M., McPhail, T., Lee, S. S. T., Kimura, S., Nebert, D. W. et al., Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 1995. 268: 722-726.
17. Veldhoen, M., Hirota, K., Westendorf, A. M., Buer, J., Dumoutier, L., Renauld, J. C. and Stockinger, B., The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 2008. 453: 106-109.
18. Nguyen, L. P. and Bradfield, C. A., The search for endogenous activators of the aryl hydrocarbon receptor. Chem. Res. Toxicol. 2008. 21: 102-116.
19. Zheng, Y., Danilenko, D. M., Valdez, P., Kasman, I., Eastham-Anderson, J., Wu, J. and Ouyang, W., Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007. 445: 648-651.
20. Rutz, S., Noubade, R., Eidenschenk, C., Ota, N., Zeng, W., Zheng, Y., Hackney, J. et al., Transcription factor c-Maf mediates the TGF-[beta]-dependent suppression of IL-22 production in TH17 cells. Nat. Immunol. 2011. 12: 1238-1245.
21. Rodgers, J., Stone, T. W., Barrett, M. P., Bradley, B. and Kennedy, P. G. E., Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis. Brain 2009. 132: 1259-1267.
22. Quintana, F. J., Basso, A. S., Iglesias, A. H., Korn, T., Farez, M. F., Bettelli, E., Caccamo, M. et al., Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature 2008. 453: 65-71.
23. Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T. et al., An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 2011. 478: 197-203.
24. Stephens, G. L., Swerdlow, B., Benjamin, E., Coyle, A. J., Humbles, A., Kolbeck, R. and Fung, M., IL-9 is a Th17-derived cytokine that limits pathogenic activity in organ-specific autoimmune disease. Eur. J. Immunol. 2011. 41: 952-962.