The roles of aryl hydrocarbon receptor in immune responses

International Immunology - Tập 25 Số 6 - Trang 335-343 - 2013
Nam‐Trung Nguyen1, Hamza Hanieh1, Taisuke Nakahama1, Tadamitsu Kishimoto1
1#N#Laboratory of Immune Regulation, WPI-Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan#N#

Tóm tắt

AbstractA number of recent studies have examined the functions of aryl hydrocarbon receptor (Ahr) in the immune system. Also known as dioxin receptor, Ahr is a ligand-activated transcription factor that serves as a receptor for various environmental toxins. The functions of Ahr in T cells depend on the specific ligand bound to the receptor. For instance, binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to Ahr suppresses experimental autoimmune encephalomyelitis (EAE) by promoting the development of Foxp3+ Treg cells, whereas 6-formylindolo[3,2-b]carbazole enhances EAE by inducing the differentiation of IL-17-producing T cells. Furthermore, specifically deleting Ahr in T cells inhibits collagen-induced arthritis in mice. In macrophages and dendritic cells (DCs), Ahr is anti-inflammatory. In response to LPS, Ahr-deficient macrophages show increased production of pro-inflammatory cytokines, such as IL-6 and TNF-α, and Ahr-deficient DCs produce less of the anti-inflammatory cytokine IL-10. In this review, we discuss the roles of Ahr in macrophages and T cells. Moreover, studies examining Ahr activation in other cell types have revealed additional contributions to B cell and osteoblast/osteoclast differentiation. We also briefly summarize the current understanding of regulatory mechanisms underlying Ahr activation in various cells and discuss the potential clinical implications of cell-specific targeting of Ahr in pathologic conditions of the immune system.

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Tài liệu tham khảo

Perdew, 1988, Association of the Ah receptor with the 90-kDa heat shock protein, J. Biol. Chem, 263, 13802, 10.1016/S0021-9258(18)68314-0

Kazlauskas, 1999, Evidence that the co-chaperone p23 regulates ligand responsiveness of the dioxin (aryl hydrocarbon) receptor, J. Biol. Chem, 274, 13519, 10.1074/jbc.274.19.13519

Ma, 1997, A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin, J. Biol. Chem, 272, 8878, 10.1074/jbc.272.14.8878

Sogawa, 1997, Ah receptor, a novel ligand-activated transcription factor, J. Biochem, 122, 1075, 10.1093/oxfordjournals.jbchem.a021864

Burbach, 1992, Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor, Proc. Natl Acad. Sci. USA, 89, 8185, 10.1073/pnas.89.17.8185

Schrenk, 1998, Impact of dioxin-type induction of drug-metabolizing enzymes on the metabolism of endo- and xenobiotics, Biochem. Pharmacol, 55, 1155

Tomita, 2003, T cell-specific disruption of arylhydrocarbon receptor nuclear translocator (Arnt) gene causes resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymic involution, J. Immunol, 171, 4113, 10.4049/jimmunol.171.8.4113

Mimura, 1999, Identification of a novel mechanism of regulation of Ah (dioxin) receptor function, Genes Dev, 13, 20, 10.1101/gad.13.1.20

Sun, 2004, Comparative analysis of dioxin response elements in human, mouse and rat genomic sequences, Nucleic Acids Res, 32, 4512, 10.1093/nar/gkh782

Ohtake, 2007, Dioxin receptor is a ligand-dependent E3 ubiquitin ligase, Nature, 446, 562, 10.1038/nature05683

Ohtake, 2009, AhR acts as an E3 ubiquitin ligase to modulate steroid receptor functions, Biochem. Pharmacol, 77, 474, 10.1016/j.bcp.2008.08.034

Mimura, 2003, Functional role of AhR in the expression of toxic effects by TCDD, Biochim. Biophys. Acta, 1619, 263, 10.1016/S0304-4165(02)00485-3

Baba, 2005, Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction, Mol. Cell Biol, 25, 10040, 10.1128/MCB.25.22.10040-10051.2005

Weiss, 2005, TCDD induces c-jun expression via a novel Ah (dioxin) receptor-mediated p38-MAPK-dependent pathway, Oncogene, 24, 4975, 10.1038/sj.onc.1208679

Nguyen, 2008, The search for endogenous activators of the aryl hydrocarbon receptor, Chem. Res. Toxicol, 21, 102, 10.1021/tx7001965

DiNatale, 2010, Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling, Toxicol. Sci, 115, 89, 10.1093/toxsci/kfq024

Kerkvliet, 2012, TCDD: an environmental immunotoxicant reveals a novel pathway of immunoregulation–a 30-year odyssey, Toxicol. Pathol, 40, 138, 10.1177/0192623311427710

Opitz, 2007, Tryptophan degradation in autoimmune diseases, Cell Mol. Life Sci, 64, 2542, 10.1007/s00018-007-7140-9

Kimura, 2008, Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells, Proc. Natl Acad. Sci. USA, 105, 9721, 10.1073/pnas.0804231105

Veldhoen, 2008, The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins, Nature, 453, 106, 10.1038/nature06881

Quintana, 2008, Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor, Nature, 453, 65, 10.1038/nature06880

Kimura, 2010, IL-6: regulator of Treg/Th17 balance, Eur. J. Immunol, 40, 1830, 10.1002/eji.201040391

Kishimoto, 2010, IL-6: from its discovery to clinical applications, Int. Immunol, 22, 347, 10.1093/intimm/dxq030

Korn, 2009, IL-17 and Th17 cells, Annu. Rev. Immunol, 27, 485, 10.1146/annurev.immunol.021908.132710

Cui, 2011, Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation, J. Clin. Invest, 121, 658, 10.1172/JCI42974

Veldhoen, 2009, Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells, J. Exp. Med, 206, 43, 10.1084/jem.20081438

Apetoh, 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, 10.1038/ni.1912

Mezrich, 2010, An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells, J. Immunol, 185, 3190, 10.4049/jimmunol.0903670

Quintana, 2010, An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis, Proc. Natl Acad. Sci. USA, 107, 20768, 10.1073/pnas.1009201107

Nakahama, 2011, Aryl hydrocarbon receptor deficiency in T cells suppresses the development of collagen-induced arthritis, Proc. Natl Acad. Sci. USA, 108, 14222, 10.1073/pnas.1111786108

Jäger, 2010, Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation, Scand. J. Immunol, 72, 173, 10.1111/j.1365-3083.2010.02432.x

Stockinger, 2009, Beyond toxicity: aryl hydrocarbon receptor-mediated functions in the immune system, J. Biol, 8, 61, 10.1186/jbiol170

Stevens, 2009, The aryl hydrocarbon receptor: a perspective on potential roles in the immune system, Immunology, 127, 299, 10.1111/j.1365-2567.2009.03054.x

Moriguchi, 2003, Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse, Proc. Natl Acad. Sci. USA, 100, 5652, 10.1073/pnas.1037886100

Martin, 2009, Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals, Immunity, 31, 321, 10.1016/j.immuni.2009.06.020

Geboes, 2009, Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice, Arthritis Rheum, 60, 390, 10.1002/art.24220

Zenewicz, 2008, Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease, Immunity, 29, 947, 10.1016/j.immuni.2008.11.003

Monteleone, 2011, Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract, Gastroenterology, 141, 237, 10.1053/j.gastro.2011.04.007

Kimura, 2009, Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses, J. Exp. Med, 206, 2027, 10.1084/jem.20090560

Sekine, 2009, Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock, Mol. Cell Biol, 29, 6391, 10.1128/MCB.00337-09

Masuda, 2011, Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages, Int. Immunol, 23, 637, 10.1093/intimm/dxr072

Biswas, 2010, Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm, Nat. Immunol, 11, 889, 10.1038/ni.1937

Gao, 2002, Regulation of gene expression in mouse macrophages stimulated with bacterial CpG-DNA and lipopolysaccharide, J. Leukoc. Biol, 72, 1234, 10.1189/jlb.72.6.1234

Matsunawa, 2009, The aryl hydrocarbon receptor activator benzo[a]pyrene enhances vitamin D3 catabolism in macrophages, Toxicol. Sci, 109, 50, 10.1093/toxsci/kfp044

Monteiro, 2007, AhR- and c-maf-dependent induction of beta7-integrin expression in human macrophages in response to environmental polycyclic aromatic hydrocarbons, Biochem. Biophys. Res. Commun, 358, 442, 10.1016/j.bbrc.2007.04.111

Farstad, 1996, Distribution of beta 7 integrins in human intestinal mucosa and organized gut-associated lymphoid tissue, Immunology, 89, 227, 10.1046/j.1365-2567.1996.d01-727.x

Veldhoen, 2010, Interferon regulatory factor 4: combinational control of lymphocyte differentiation, Immunity, 33, 141, 10.1016/j.immuni.2010.08.007

Brüstle, 2007, The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4, Nat. Immunol, 8, 958, 10.1038/ni1500

Honma, 2005, Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS, Proc. Natl Acad. Sci. USA, 102, 16001, 10.1073/pnas.0504226102

Negishi, 2005, Negative regulation of Toll-like-receptor signaling by IRF-4, Proc. Natl Acad. Sci. USA, 102, 15989, 10.1073/pnas.0508327102

Satoh, 2010, The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection, Nat. Immunol, 11, 936, 10.1038/ni.1920

Belz, 2012, Transcriptional programming of the dendritic cell network, Nat. Rev. Immunol, 12, 101, 10.1038/nri3149

Vogel, 2008, Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase, Biochem. Biophys. Res. Commun, 375, 331, 10.1016/j.bbrc.2008.07.156

Nguyen, 2010, Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism, Proc. Natl Acad. Sci. USA, 107, 19961, 10.1073/pnas.1014465107

Thatcher, 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, 10.2353/ajpath.2007.060391

Kerkvliet, 2009, AHR-mediated immunomodulation: the role of altered gene transcription, Biochem. Pharmacol, 77, 746, 10.1016/j.bcp.2008.11.021

Bankoti, 2010, Functional and phenotypic effects of AhR activation in inflammatory dendritic cells, Toxicol. Appl. Pharmacol, 246, 18, 10.1016/j.taap.2010.03.013

Wu, 2011, AhR deficiency impairs expression of LPS-induced inflammatory genes in mice, Biochem. Biophys. Res. Commun, 410, 358, 10.1016/j.bbrc.2011.06.018

Mellor, 2004, IDO expression by dendritic cells: tolerance and tryptophan catabolism, Nat. Rev. Immunol, 4, 762, 10.1038/nri1457

Desvignes, 2009, Interferon-gamma-responsive nonhematopoietic cells regulate the immune response to Mycobacterium tuberculosis, Immunity, 31, 974, 10.1016/j.immuni.2009.10.007

Sulentic, 2011, The long winding road toward understanding the molecular mechanisms for B-cell suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin, Toxicol. Sci, 120, S171, 10.1093/toxsci/kfq324

Sulentic, 1998, Aryl hydrocarbon receptor-dependent suppression by 2,3,7, 8-tetrachlorodibenzo-p-dioxin of IgM secretion in activated B cells, Mol. Pharmacol, 53, 623, 10.1124/mol.53.4.623

De Abrew, 2011, Regulation of Bach2 by the aryl hydrocarbon receptor as a mechanism for suppression of B-cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin, Toxicol. Appl. Pharmacol, 252, 150, 10.1016/j.taap.2011.01.020

De Abrew, 2010, An integrated genomic analysis of aryl hydrocarbon receptor-mediated inhibition of B-cell differentiation, Toxicol. Sci, 118, 454, 10.1093/toxsci/kfq265

Tanaka, 2005, Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells, Int. Immunol, 17, 797, 10.1093/intimm/dxh260

Boverhof, 2004, 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells, Mol. Pharmacol, 66, 1662, 10.1124/mol.104.002915

Thurmond, 2000, The aryl hydrocarbon receptor has a role in the in vivo maturation of murine bone marrow B lymphocytes and their response to 2,3,7,8-tetrachlorodibenzo-p-dioxin, Toxicol. Appl. Pharmacol, 165, 227, 10.1006/taap.2000.8942

Lu, 2010, Induction of the aryl hydrocarbon receptor-responsive genes and modulation of the immunoglobulin M response by 2,3,7,8-tetrachlorodibenzo-p-dioxin in primary human B cells, Toxicol. Sci, 118, 86, 10.1093/toxsci/kfq234

Jux, 2009, Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice, J. Immunol, 182, 6709, 10.4049/jimmunol.0713344

Kadow, 2011, Aryl hydrocarbon receptor is critical for homeostasis of invariant gammadelta T cells in the murine epidermis, J. Immunol, 187, 3104, 10.4049/jimmunol.1100912

Ikuta, 2010, B lymphocyte-induced maturation protein 1 is a novel target gene of aryl hydrocarbon receptor, J. Dermatol. Sci, 58, 211, 10.1016/j.jdermsci.2010.04.003

Tsuji, 2012, Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: the basis of its anti-inflammatory effect, J. Invest. Dermatol, 132, 59, 10.1038/jid.2011.194

Platten, 2005, Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite, Science, 310, 850, 10.1126/science.1117634

Opitz, 2011, An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor, Nature, 478, 197, 10.1038/nature10491

Dolusić, 2011, Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators, J. Med. Chem, 54, 5320, 10.1021/jm2006782

Röhrig, 2010, Rational design of indoleamine 2,3-dioxygenase inhibitors, J. Med. Chem, 53, 1172, 10.1021/jm9014718

Lee, 2012, AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch, Nat. Immunol, 13, 144, 10.1038/ni.2187

Lee, 2012, AHR and the transcriptional regulation of type-17/22 ILC, Front. Immunol, 3, 10, 10.3389/fimmu.2012.00010

Qiu, 2012, The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells, Immunity, 36, 92, 10.1016/j.immuni.2011.11.011

Li, 2011, Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation, Cell, 147, 629, 10.1016/j.cell.2011.09.025

Sakai, 2003, TCDD treatment eliminates the long-term reconstitution activity of hematopoietic stem cells, Toxicol. Sci, 72, 84, 10.1093/toxsci/kfg002

Boitano, 2010, Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells, Science, 329, 1345, 10.1126/science.1191536

Korkalainen, 2009, Dioxins interfere with differentiation of osteoblasts and osteoclasts, Bone, 44, 1134, 10.1016/j.bone.2009.02.019

Jensen, 2003, Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study, Environ. Health, 2, 16, 10.1186/1476-069X-2-16

Singh, 2011, Aryl hydrocarbon receptor-null allele mice have hematopoietic stem/progenitor cells with abnormal characteristics and functions, Stem Cells Dev, 20, 769, 10.1089/scd.2010.0333

Casado, 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, 10.1124/mol.111.071381

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International Immunology

Tập 25 Số 6

335-343

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