Abstract
Aryl hydrocarbon receptor (AhR), a type of transcriptional factor, is widely expressed in immune cells. The activation of AhR signaling pathway depends on its ligands, which exist in environment and can also be produced by metabolism. Normal expressions of AhR and AhR-mediated signaling may be essential for immune responses, and effects of AhR signaling on the development and function of innate and adaptive immune cells have also been revealed in previous studies. Recent studies also indicate that aberrant AhR signaling may be related to autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), autoimmune uveitis (AU), autoimmune diabetes, Behcet’s disease (BD) and myasthenia gravis (MG). Moreover, administration of AhR ligands or drugs has been proven effective for improving pathological outcomes in some autoimmune diseases or models. In this review, we summarize the effects of AhR on several innate and adaptive immune cells associated with autoimmunity, and the mechanism on how AhR participates in autoimmune diseases. In addition, we also discuss therapeutic potential and application prospect of AhR in autoimmune diseases, so as to provide valuable information for exploring novel and effective approaches to autoimmune disease treatments.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abdullah A, Maged M, Hairul-Islam MI, Osama IA, Maha H, Manal A, Hamza H (2019) Activation of aryl hydrocarbon receptor signaling by a novel agonist ameliorates autoimmune encephalomyelitis. PLoS One 14:0215981. https://doi.org/10.1371/journal.pone.0215981
Ahmadi H, Mahmoudi M, Gharibdoost F, Vojdanian M, Jamshidi AR, Fattahi MJ, Aghazadeh Z et al (2018) Targeting of circulating Th17 cells by beta-d-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis. Inflammopharmacology 26:57–65. https://doi.org/10.1007/s10787-017-0410-8
Allan LL, Sherr DH (2005) Constitutive activation and environmental chemical induction of the aryl hydrocarbon receptor/transcription factor in activated human B lymphocytes. Mol Pharmacol 67:1740–1750. https://doi.org/10.1124/mol.104.009100
Ambrosio LF, Insfran C, Volpini X, Acosta Rodriguez E, Serra HM, Quintana FJ, Cervi L et al (2019) Role of Aryl hydrocarbon receptor (AhR) in the regulation of immunity and immunopathology during trypanosoma cruzi infection. Front Immunol 10:631. https://doi.org/10.3389/fimmu.2019.00631
Apetoh L, Quintana FJ, Pot C, Joller N, Xiao S, Kumar D, Burns EJ et al (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. https://doi.org/10.1038/ni.1912
Bai Y, Liu R, Huang D, La Cava A, Tang YY, Iwakura Y, Campagnolo DI et al (2008) CCL2 recruitment of IL-6-producing CD11b + monocytes to the draining lymph nodes during the initiation of Th17-dependent B cell-mediated autoimmunity. Eur J Immunol 38:1877–1888. https://doi.org/10.1002/eji.200737973
Balandina A, Lecart S, Dartevelle P, Saoudi A, Berrih-Aknin S (2005) Functional defect of regulatory CD4(+)CD25 + T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 105:735–741. https://doi.org/10.1182/blood-2003-11-3900
Baricza E, Tamási V, Marton N, Buzás EI, Nagy G (2015) The emerging role of aryl hydrocarbon receptor in the activation and differentiation of Th17 cells. Cell Mol Life Sci 73:95–117. https://doi.org/10.1007/s00018-015-2056-2
Bernatsky S, Smargiassi A, Johnson M, Kaplan GG, Barnabe C, Svenson L, Brand A et al (2015) Fine particulate air pollution, nitrogen dioxide, and systemic autoimmune rheumatic disease in Calgary, Alberta. Environ Res 140:474–478. https://doi.org/10.1016/j.envres.2015.05.007
Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238. https://doi.org/10.1038/nature04753
Bjartmar C, Trapp BD (2003) Axonal degeneration and progressive neurologic disability in multiple sclerosis. Neurotox Res 5:157–164
Bonfioli AA, Orefice F (2005) Behcet’s disease. Semin Ophthalmol 20:199–206. https://doi.org/10.1080/08820530500231953
Buhrmann C, Mobasheri A, Matis U, Shakibaei M (2010) Curcumin mediated suppression of nuclear factor-kappaB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment. Arthritis Res Ther 12:127. https://doi.org/10.1186/ar3065
Caspi RR (2010) A look at autoimmunity and inflammation in the eye. J Clin Invest 120:3073–3083. https://doi.org/10.1172/JCI42440
Celhar T, Fairhurst AM (2014) Toll-like receptors in systemic lupus erythematosus: potential for personalized treatment. Front Pharmacol 5:265. https://doi.org/10.3389/fphar.2014.00265
Cervantes-Barragan L, Colonna M (2018) AHR signaling in the development and function of intestinal immune cells and beyond. Semin Immunopathol 40:371–377. https://doi.org/10.1007/s00281-018-0694-9
Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, Bowcock AM (2000) JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 106:R75–81. https://doi.org/10.1172/jci11679
Chen CJ, Chang SJ (2013) Purinergic signaling during inflammation. N Engl J Med 368:1260–1260. https://doi.org/10.1056/nejmc1300259
Cho Y-G, Cho M-L, Min S-Y, Kim H-Y (2007) Type II collagen autoimmunity in a mouse model of human rheumatoid arthritis. Autoimmun Rev 7:65–70. https://doi.org/10.1016/j.autrev.2007.08.001
Chuang HC, Tsai CY, Hsueh CH, Tan TH (2018) GLK-IKKbeta signaling induces dimerization and translocation of the AhR-RORgammat complex in IL-17A induction and autoimmune disease. Sci Adv 4:eaat5401. https://doi.org/10.1126/sciadv.aat5401
Clemente JC, Manasson J, Scher JU (2018) The role of the gut microbiome in systemic inflammatory disease. BMJ 360:5145. https://doi.org/10.1136/bmj.j5145
Climaco-Arvizu S, Dominguez-Acosta O, Cabanas-Cortes MA, Rodriguez-Sosa M, Gonzalez FJ, Vega L, Elizondo G (2016) Aryl hydrocarbon receptor influences nitric oxide and arginine production and alters M1/M2 macrophage polarization. Life Sci 155:76–84. https://doi.org/10.1016/j.lfs.2016.05.001
Collison J (2018) AhR controls tolerance to cell debris. Nat Rev Rheumatol 14:384. https://doi.org/10.1038/s41584-018-0024-6
Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM, Belkaid Y, Powrie F (2007) A functionally specialized population of mucosal CD103 + DCs induces Foxp3 + regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 204:1757–1764. https://doi.org/10.1084/jem.20070590
Coutant F, Miossec P (2016) Altered dendritic cell functions in autoimmune diseases: distinct and overlapping profiles. Nat Rev Rheumatol 12:703–715. https://doi.org/10.1038/nrrheum.2016.147
Crow MK (2014) Type I interferon in the pathogenesis of lupus. J Immunol 192:5459–5468. https://doi.org/10.4049/jimmunol.1002795
Curran CS, Gupta S, Sanz I, Sharon E (2019) PD-1 immunobiology in systemic lupus erythematosus. J Autoimmun 97:1–9. https://doi.org/10.1016/j.jaut.2018.10.025
Deng YN, Bellanti JA, Zheng SG (2019) Essential kinases and transcriptional regulators and their roles in autoimmunity. Biomolecules 9:145. https://doi.org/10.3390/biom9040145
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
DiNatale BC, Murray IA, Schroeder JC, Flaveny CA, Lahoti TS, Laurenzana EM, Omiecinski CJ et al (2010) Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol Sci 115:89–97. https://doi.org/10.1093/toxsci/kfq024
Dieker J, Tel J, Pieterse E, Thielen A, Rother N, Bakker M, Fransen J et al (2016) Circulating apoptotic microparticles in systemic lupus erythematosus patients drive the activation of dendritic cell subsets and prime neutrophils for NETosis. Arthritis Rheumatol 68:462–472. https://doi.org/10.1002/art.39417
Dong C (2008) TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 8:337–348. https://doi.org/10.1038/nri2295
D’Alise AM, Ergun A, Hill JA, Mathis D, Benoist C (2011) A cluster of coregulated genes determines TGF-beta-induced regulatory T-cell (Treg) dysfunction in NOD mice. Proc Natl Acad Sci USA 108:8737–8742. https://doi.org/10.1073/pnas.1105364108
Egwuagu CE (2009) STAT3 in CD4 + T helper cell differentiation and inflammatory diseases. Cytokine 47:149–156. https://doi.org/10.1016/j.cyto.2009.07.003
Esser C, Rannug A, Stockinger B (2009) The aryl hydrocarbon receptor in immunity. Trends Immunol 30:447–454. https://doi.org/10.1016/j.it.2009.06.005
Finlay DK, Rosenzweig E, Sinclair LV, Feijoo-Carnero C, Hukelmann JL, Rolf J, Panteleyev AA et al (2012) PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8 + T cells. J Exp Med 209:2441–2453. https://doi.org/10.1084/jem.20112607
Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4 + CD25 + regulatory T cells. Nat Immunol 4:330–336. https://doi.org/10.1038/ni904
Fu J, Nogueira SV, Drongelen VV, Coit P, Ling S, Rosloniec EF, Sawalha AH et al (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. https://doi.org/10.1073/pnas.1722124115
Fuhua P, Xuhui D, Zhiyang Z, Ying J, Yu Y, Feng T, Jia L et al (2012) Antioxidant status of bilirubin and uric acid in patients with myasthenia gravis. NeuroImmunoModulation 19:43–49. https://doi.org/10.1159/000327727
Furman DP, Oshchepkova EA, Oshchepkov DY, Shamanina MY, Mordvinov VA (2009) Promoters of the genes encoding the transcription factors regulating the cytokine gene expression in macrophages contain putative binding sites for aryl hydrocarbon receptor. Comput Biol Chem 33:465–468. https://doi.org/10.1016/j.compbiolchem.2009.10.004
Gandhi R, Kumar D, Burns EJ, Nadeau M, Dake B, Laroni A, Kozoriz D et al (2010a) Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell–like and Foxp3 + regulatory T cells. Nat Immunol 11:846–853. https://doi.org/10.1038/ni.1915
Gandhi R, Kumar D, Burns EJ, Nadeau M, Dake B, Laroni A, Kozoriz D et al (2010b) Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells. Nat Immunol 11:846–853. https://doi.org/10.1038/ni.1915
Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel JE, Ramos HL et al (2010) Generation of pathogenic T(H)17 cells in the absence of TGF-beta signaling. Nature 467:967–971. https://doi.org/10.1038/nature09447
Goudot C, Coillard A, Villani AC, Gueguen P, Cros A, Sarkizova S, Tang-Huau TL et al (2017) Aryl hydrocarbon receptor controls monocyte differentiation into dendritic cells versus macrophages. Immunity 47:582–596. https://doi.org/10.1016/j.immuni.2017.08.016(e586)
Gradolatto A, Nazzal D, Truffault F, Bismuth J, Fadel E, Foti M, Berrih-Aknin S (2014) Both Treg cells and Tconv cells are defective in the Myasthenia gravis thymus: roles of IL-17 and TNF-alpha. J Autoimmun 52:53–63. https://doi.org/10.1016/j.jaut.2013.12.015
Green MR, Monti S, Dalla-Favera R, Pasqualucci L, Walsh NC, Schmidt-Supprian M, Kutok JL et al (2011) Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program. Proc Natl Acad Sci USA 108:2873–2878. https://doi.org/10.1073/pnas.1019537108
van Grevenynghe J, Bernard M, Langouet S, Le Berre C, Fest T, Fardel O (2005) Human CD34-positive hematopoietic stem cells constitute targets for carcinogenic polycyclic aromatic hydrocarbons. J Pharmacol Exp Ther 314:693–702. https://doi.org/10.1124/jpet.105.084780
Guan SY, Liu LN, Mao YM, Zhao CN, Wu Q, Dan YL, Bellua Sam N et al (2019) Association between interleukin 35 gene single nucleotide polymorphisms and systemic lupus erythematosus in a Chinese Han population. Biomolecules 9:157. https://doi.org/10.3390/biom9040157
Gutierrez-Vazquez C, Quintana FJ (2018) Regulation of the immune response by the Aryl hydrocarbon receptor. Immunity 48:19–33. https://doi.org/10.1016/j.immuni.2017.12.012
Hao J, Liu R, Piao W, Zhou Q, Vollmer TL, Campagnolo DI, Xiang R et al (2010) Central nervous system (CNS)-resident natural killer cells suppress Th17 responses and CNS autoimmune pathology. J Exp Med 207:1907–1921. https://doi.org/10.1084/jem.20092749
Hao N, Whitelaw ML (2013) The emerging roles of AhR in physiology and immunity. Biochem Pharmacol 86:561–570. https://doi.org/10.1016/j.bcp.2013.07.004
He CX, Prevot N, Boitard C, Avner P, Rogner UC (2010) Inhibition of type 1 diabetes by upregulation of the circadian rhythm-related aryl hydrocarbon receptor nuclear translocator-like 2. Immunogenetics 62:585–592. https://doi.org/10.1007/s00251-010-0467-7
Hirahara K, Ghoreschi K, Laurence A, Yang XP, Kanno Y, O’Shea JJ (2010) Signal transduction pathways and transcriptional regulation in Th17 cell differentiation. Cytokine Growth Factor Rev 21:425–434. https://doi.org/10.1016/j.cytogfr.2010.10.006
Huang Y, He J, Liang H, Hu K, Jiang S, Yang L, Mei S et al (2018) Aryl hydrocarbon receptor regulates apoptosis and inflammation in a murine model of experimental autoimmune uveitis. Front Immunol 9:1713. https://doi.org/10.3389/fimmu.2018.01713
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 225:130–138. https://doi.org/10.1016/j.toxlet.2013.11.027
Inshaw JRJ, Cutler AJ, Burren OS, Stefana MI, Todd JA (2018) Approaches and advances in the genetic causes of autoimmune disease and their implications. Nat Immunol 19:674–684. https://doi.org/10.1038/s41590-018-0129-8
Jux B, Kadow S, Esser C (2009) Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice. J Immunol 182:6709–6717. https://doi.org/10.4049/jimmunol.0713344
Kadowaki A, Miyake S, Saga R, Chiba A, Mochizuki H, Yamamura T (2016) Gut environment-induced intraepithelial autoreactive CD4(+) T cells suppress central nervous system autoimmunity via LAG-3. Nat Commun 7:11639. https://doi.org/10.1038/ncomms11639
Kastrukoff LF, Lau A, Wee R, Zecchini D, White R, Paty DW (2003) Clinical relapses of multiple sclerosis are associated with ‘novel’ valleys in natural killer cell functional activity. J Neuroimmunol 145:103–114. https://doi.org/10.1016/j.jneuroim.2003.10.001
Kaye J, Piryatinsky V, Birnberg T, Hingaly T, Raymond E, Kashi R, Amit-Romach E et al (2016) Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 113:E6145–e6152. https://doi.org/10.1073/pnas.1607843113
Kazlauskas A, Poellinger L, Pongratz I (2000) The immunophilin-like protein XAP2 regulates ubiquitination and subcellular localization of the dioxin receptor. J Biol Chem 275:41317–41324. https://doi.org/10.1074/jbc.M007765200
Kimura A, Naka T, Nakahama T, Chinen I, Masuda K, Nohara K, Fujii-Kuriyama Y et al (2009) Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses. J Exp Med 206:2027–2035. https://doi.org/10.1084/jem.20090560
Kimura A, Naka T, Nohara K, Fujii-Kuriyama Y, Kishimoto T (2008a) Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells. Proc Natl Acad Sci USA 105:9721–9726. https://doi.org/10.1073/pnas.0804231105
Kimura A, Naka T, Nohara K, Fujii-Kuriyama Y, Kishimoto T (2008b) Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells. Proc Natl Acad Sci 105:9721–9726. https://doi.org/10.1073/pnas.0804231105
Klareskog L, Padyukov L, Lorentzen J, Alfredsson L (2006) Mechanisms of disease: genetic susceptibility and environmental triggers in the development of rheumatoid arthritis. Nat Clin Pract Rheumatol 2:425–433. https://doi.org/10.1038/ncprheum0249
Kovalova N, Manzan M, Crawford R, Kaminski N (2016) Role of aryl hydrocarbon receptor polymorphisms on TCDD-mediated CYP1B1 induction and IgM suppression by human B cells. Toxicol Appl Pharmacol 309:15–23. https://doi.org/10.1016/j.taap.2016.08.011
Lahoti TS, Hughes JM, Kusnadi A, John K, Zhu B, Murray IA, Gowda K et al (2013b) Aryl hydrocarbon receptor antagonism attenuates growth factor expression, proliferation, and migration in fibroblast-like synoviocytes from patients with rheumatoid arthritis. J Pharmacol Exp Ther 348:236–245. https://doi.org/10.1124/jpet.113.209726
Lahoti TS, John K, Hughes JM, Kusnadi A, Murray IA, Krishnegowda G, Amin S et al (2013a) Aryl hydrocarbon receptor antagonism mitigates cytokine-mediated inflammatory signaling in primary human fibroblast-like synoviocytes. Ann Rheum Dis 72:1708–1716. https://doi.org/10.1136/annrheumdis-2012-202639
Larigot L, Juricek L, Dairou J, Coumoul X (2018) AhR signaling pathways and regulatory functions. Biochim Open 7:1–9. https://doi.org/10.1016/j.biopen.2018.05.001
Laurence A, Amarnath S, Mariotti J, Kim YC, Foley J, Eckhaus M, O’Shea JJ et al (2012) STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft-versus-host disease. Immunity 37:209–222. https://doi.org/10.1016/j.immuni.2012.05.027
Lawrence BP, Vorderstrasse BA (2013) New insights into the aryl hydrocarbon receptor as a modulator of host responses to infection. Semin Immunopathol 35:615–626. https://doi.org/10.1007/s00281-013-0395-3
Lee Y-H, Lin C-H, Hsu P-C, Sun Y-Y, Huang Y-J, Zhuo J-H, Wang C-Y et al (2015) Aryl hydrocarbon receptor mediates both pro-inflammatory and anti-inflammatory effects in lipopolysaccharide-activated microglia. Glia 63:1138–1154. https://doi.org/10.1002/glia.22805
Li J, McMurray RW (2009) Effects of chronic exposure to DDT and TCDD on disease activity in murine systemic lupus erythematosus. Lupus 18:941–949. https://doi.org/10.1177/0961203309104431
Lindsey S, Papoutsakis ET (2011) The aryl hydrocarbon receptor (AHR) transcription factor regulates megakaryocytic polyploidization. Br J Haematol 152:469–484. https://doi.org/10.1111/j.1365-2141.2010.08548.x
Liu R, Hao J, Dayao CS, Shi FD, Campagnolo DI (2009) T-bet deficiency decreases susceptibility to experimental myasthenia gravis. Exp Neurol 220:366–373. https://doi.org/10.1016/j.expneurol.2009.09.022
London A, Benhar I, Mattapallil MJ, Mack M, Caspi RR, Schwartz M (2013) Functional macrophage heterogeneity in a mouse model of autoimmune central nervous system pathology. J Immunol 190:3570–3578. https://doi.org/10.4049/jimmunol.1202076
Loots GG, Ovcharenko I (2007) Mulan: multiple-sequence alignment to predict functional elements in genomic sequences. Methods Mol Biol 395:237–254
Mann KK, Matulka RA, Hahn ME, Trombino AF, Lawrence BP, Kerkvliet NI, Sherr DH (1999) The role of polycyclic aromatic hydrocarbon metabolism in dimethylbenz[a]anthracene-induced pre-B lymphocyte apoptosis. Toxicol Appl Pharmacol 161:10–22. https://doi.org/10.1006/taap.1999.8778
Marshall NB, Kerkvliet NI (2010) Dioxin and immune regulation: emerging role of aryl hydrocarbon receptor in the generation of regulatory T cells. Ann N Y Acad Sci 1183:25–37. https://doi.org/10.1111/j.1749-6632.2009.05125.x
Mascanfroni ID, Takenaka MC, Yeste A, Patel B, Wu Y, Kenison JE, Siddiqui S et al (2015) Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-alpha. Nat Med 21:638–646. https://doi.org/10.1038/nm.3868
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 77:608–626. https://doi.org/10.1016/j.bcp.2008.10.013
Matsuoka N, Eguchi K, Kawakami A, Tsuboi M, Kawabe Y, Aoyagi T, Nagataki S (1996) Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells. Clin Exp Immunol 104:501–508. https://doi.org/10.1046/j.1365-2249.1996.46752.x
Mayo L, Trauger SA, Blain M, Nadeau M, Patel B, Alvarez JI, Mascanfroni ID et al (2014) Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat Med 20:1147–1156. https://doi.org/10.1038/nm.3681
McGuire J, Whitelaw ML, Pongratz I, Gustafsson JA, Poellinger L (1994) A cellular factor stimulates ligand-dependent release of hsp90 from the basic helix-loop-helix dioxin receptor. Mol Cell Biol 14:2438–2446. https://doi.org/10.1128/mcb.14.4.2438
McMillan BJ, Bradfield CA (2007) The aryl hydrocarbon receptor sans xenobiotics: endogenous function in genetic model systems. Mol Pharmacol 72:487–498. https://doi.org/10.1124/mol.107.037259
Meng X, Fang S, Zhang Z, Wang Y, You C, Zhang J, Yan H (2017) Preventive effect of chrysin on experimental autoimmune uveitis triggered by injection of human IRBP peptide 1-20 in mice. Cell Mol Immunol 14:702–711. https://doi.org/10.1038/cmi.2015.107
Meriggioli MN, Sanders DB (2009) Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 8:475–490. https://doi.org/10.1016/s1474-4422(09)70063-8
Miani M, Le Naour J, Waeckel-Enee E, Verma SC, Straube M, Emond P, Ryffel B et al (2018) Gut microbiota-stimulated innate lymphoid cells support beta-defensin 14 expression in pancreatic endocrine cells, preventing autoimmune diabetes. Cell Metab 28(557–572):556. https://doi.org/10.1016/j.cmet.2018.06.012
Migeon BR (2006) The role of X inactivation and cellular mosaicism in women’s health and sex-specific diseases. JAMA 295:1428–1433. https://doi.org/10.1001/jama.295.12.1428
Miller FW, Alfredsson L, Costenbader KH, Kamen DL, Nelson LM, Norris JM, De Roos AJ (2012) Epidemiology of environmental exposures and human autoimmune diseases: findings from a national institute of environmental health sciences expert panel workshop. J Autoimmun 39:259–271. https://doi.org/10.1016/j.jaut.2012.05.002
Mimura J, Ema M, Sogawa K, Fujii-Kuriyama Y (1999) Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev 13:20–25. https://doi.org/10.1101/gad.13.1.20
Mitchell KA, Elferink CJ (2009) Timing is everything: consequences of transient and sustained AhR activity. Biochem Pharmacol 77:947–956. https://doi.org/10.1016/j.bcp.2008.10.028
Mohammadi S, Memarian A, Sedighi S, Behnampour N, Yazdani Y (2018) Immunoregulatory effects of indole-3-carbinol on monocyte-derived macrophages in systemic lupus erythematosus: a crucial role for aryl hydrocarbon receptor. Autoimmunity 51:199–209. https://doi.org/10.1080/08916934.2018.1494161
Moon YW, Hajjar J, Hwu P, Naing A (2015) Targeting the indoleamine 2,3-dioxygenase pathway in cancer. J Immunother Cancer 3:51. https://doi.org/10.1186/s40425-015-0094-9
Morales JL, Krzeminski J, Amin S, Perdew GH (2008) Characterization of the antiallergic drugs 3-[2-(2-phenylethyl) benzoimidazole-4-yl]-3-hydroxypropanoic acid and ethyl 3-hydroxy-3-[2-(2-phenylethyl)benzoimidazol-4-yl]propanoate as full aryl hydrocarbon receptor agonists. Chem Res Toxicol 21:472–482. https://doi.org/10.1021/tx700350v
Morales JL, Perdew GH (2007) Carboxyl terminus of hsc70-interacting protein (CHIP) can remodel mature aryl hydrocarbon receptor (AhR) complexes and mediate ubiquitination of both the AhR and the 90 kDa heat-shock protein (hsp90) in vitro. Biochemistry 46:610–621. https://doi.org/10.1021/bi062165b
Morel L (2017) Immunometabolism in systemic lupus erythematosus. Nat Rev Rheumatol 13:280–290. https://doi.org/10.1038/nrrheum.2017.43
Moreno-Nieves UY, Mundy DC, Shin JH, Tam K, Sunwoo JB (2018) The aryl hydrocarbon receptor modulates the function of human CD56bright NK cells. Euro J Immunol 48:771–776. https://doi.org/10.1002/eji.201747289
Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969. https://doi.org/10.1038/nri2448
Nakahama T, Kimura A, Nguyen NT, Chinen I, Hanieh H, Nohara K, Fujii-Kuriyama Y et al (2011) Aryl hydrocarbon receptor deficiency in T cells suppresses the development of collagen-induced arthritis. Proc Natl Acad Sci USA 108:14222–14227. https://doi.org/10.1073/pnas.1111786108
Nguyen NT, Kimura A, Nakahama T, Chinen I, Masuda K, Nohara K, Fujii-Kuriyama Y et al (2010) Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc Natl Acad Sci USA 107:19961–19966. https://doi.org/10.1073/pnas.1014465107
Nguyen NT, Nakahama T, Kishimoto T (2013) Aryl hydrocarbon receptor and experimental autoimmune arthritis. Semin Immunopathol 35:637–644. https://doi.org/10.1007/s00281-013-0392-6
Niedbala W, Alves-Filho JC, Fukada SY, Vieira SM, Mitani A, Sonego F, Mirchandani A et al (2011) Regulation of type 17 helper T-cell function by nitric oxide during inflammation. Proc Natl Acad Sci USA 108:9220–9225. https://doi.org/10.1073/pnas.1100667108
Nii T, Kuzuya K, Kabata D, Matsui T, Murata A, Ohya T, Matsuoka H et al (2019) Crosstalk between tumor necrosis factor-alpha signaling and aryl hydrocarbon receptor signaling in nuclear factor -kappa B activation: a possible molecular mechanism underlying the reduced efficacy of TNF-inhibitors in rheumatoid arthritis by smoking. J Autoimmun 98:95–102. https://doi.org/10.1016/j.jaut.2018.12.004
Niven J, Hoare J, McGowan D, Devarajan G, Itohara S, Gannage M, Teismann P et al (2015) S100B up-regulates macrophage production of IL1beta and CCL22 and influences severity of retinal inflammation. PLoS One 10:e0132688. https://doi.org/10.1371/journal.pone.0132688
Nugent LF, Shi G, Vistica BP, Ogbeifun O, Hinshaw SJ, Gery I (2013) ITE, a novel endogenous nontoxic aryl hydrocarbon receptor ligand, efficiently suppresses EAU and T-cell-mediated immunity. Invest Ophthalmol Vis Sci 54:7463–7469. https://doi.org/10.1167/iovs.12-11479
Ogura N, Akutsu M, Tobe M, Sakamaki H, Abiko Y, Kondoh T (2007) Microarray analysis of IL-1beta-stimulated chemokine genes in synovial fibroblasts from human TMJ. J Oral Pathol Med 36:223–228. https://doi.org/10.1111/j.1600-0714.2007.00515.x
Oliver JE, Silman AJ (2006) Risk factors for the development of rheumatoid arthritis. Scand J Rheumatol 35:169–174. https://doi.org/10.1080/03009740600718080
Parada-Turska J, Rzeski W, Zgrajka W, Majdan M, Kandefer-Szerszen M, Turski W (2006) Kynurenic acid, an endogenous constituent of rheumatoid arthritis synovial fluid, inhibits proliferation of synoviocytes in vitro. Rheumatol Int 26:422–426. https://doi.org/10.1007/s00296-005-0057-4
Peng H, Jiang X, Chen Y, Sojka DK, Wei H, Gao X, Sun R et al (2013) Liver-resident NK cells confer adaptive immunity in skin-contact inflammation. J Clin Invest 123:1444–1456. https://doi.org/10.1172/JCI66381
Perona-Wright G, Mohrs K, Szaba FM, Kummer LW, Madan R, Karp CL, Johnson LL et al (2009) Systemic but not local infections elicit immunosuppressive IL-10 production by natural killer cells. Cell Host Microbe 6:503–512. https://doi.org/10.1016/j.chom.2009.11.003
Quintana FJ (2013) Nanoparticles for the induction of antigen-specific Tregs. Immunotherapy 5:437–440. https://doi.org/10.2217/imt.13.25
Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M et al (2008) Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453:65–71. https://doi.org/10.1038/nature06880
Quintana FJ, Murugaiyan G, Farez MF, Mitsdoerffer M, Tukpah AM, Burns EJ, Weiner HL (2010) An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 107:20768–20773. https://doi.org/10.1073/pnas.1009201107
Quintana FJ, Sherr DH (2013a) Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol Rev 65:1148–1161. https://doi.org/10.1124/pr.113.007823
Quintana FJ, Sherr DH (2013b) Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol Rev 65:1148–1161. https://doi.org/10.1124/pr.113.007823
Ravishankar B, Liu H, Shinde R, Chaudhary K, Xiao W, Bradley J, Koritzinsky M et al (2015) The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity. Proc Natl Acad Sci USA 112:10774–10779. https://doi.org/10.1073/pnas.1504276112
Ritz SA (2010) Air pollution as a potential contributor to the ‘epidemic’ of autoimmune disease. Med Hypotheses 74:110–117. https://doi.org/10.1016/j.mehy.2009.07.033
Rothhammer V, Borucki DM, Tjon EC, Takenaka MC, Chao CC, Ardura-Fabregat A, de Lima KA et al (2018) Microglial control of astrocytes in response to microbial metabolites. Nature 557:724–728. https://doi.org/10.1038/s41586-018-0119-x
Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, Chao CC et al (2016) Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med 22:586–597. https://doi.org/10.1038/nm.4106
Rothhammer V, Quintana FJ (2019) The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nat Rev Immunol 19:184–197. https://doi.org/10.1038/s41577-019-0125-8
Rouse M, Singh NP, Nagarkatti PS, Nagarkatti M (2013) Indoles mitigate the development of experimental autoimmune encephalomyelitis by induction of reciprocal differentiation of regulatory T cells and Th17 cells. Br J Pharmacol 169:1305–1321. https://doi.org/10.1111/bph.12205
Salazar F, Awuah D, Negm OH, Shakib F, Ghaemmaghami AM (2017) The role of indoleamine 2,3-dioxygenase-aryl hydrocarbon receptor pathway in the TLR4-induced tolerogenic phenotype in human DCs. Sci Rep 7:43337. https://doi.org/10.1038/srep43337
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. https://doi.org/10.1016/j.bcp.2018.02.031
Schulz VJ, Smit JJ, Bol-Schoenmakers M, van Duursen MB, van den Berg M, Pieters RH (2012) 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 215:100–109. https://doi.org/10.1016/j.toxlet.2012.09.024
Selmi C, Lu Q, Humble MC (2012) Heritability versus the role of the environment in autoimmunity. J Autoimmun 39:249–252. https://doi.org/10.1016/j.jaut.2012.07.011
Sherr DH, Monti S (2013) The role of the aryl hydrocarbon receptor in normal and malignant B cell development. Semin Immunopathol 35:705–716. https://doi.org/10.1007/s00281-013-0390-8
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. https://doi.org/10.1073/pnas.1302856110
Shinde R, Hezaveh K, Halaby MJ, Kloetgen A, Chakravarthy A, da Silva Medina T, Deol R et al (2018) Apoptotic cell-induced AhR activity is required for immunological tolerance and suppression of systemic lupus erythematosus in mice and humans. Nat Immunol 19:571–582. https://doi.org/10.1038/s41590-018-0107-1
Shinde R, McGaha TL (2018) The Aryl hydrocarbon receptor: connecting immunity to the microenvironment. Trends Immunol 39:1005–1020. https://doi.org/10.1016/j.it.2018.10.010
Stockinger B (2009) Beyond toxicity: aryl hydrocarbon receptor-mediated functions in the immune system. J Biol 8:61. https://doi.org/10.1186/jbiol170
Stockinger B, Hirota K, Duarte J, Veldhoen M (2011) External influences on the immune system via activation of the aryl hydrocarbon receptor. Semin Immunol 23:99–105. https://doi.org/10.1016/j.smim.2011.01.008
Stockinger B, Di Meglio P, Gialitakis M, Duarte JH (2014) The aryl hydrocarbon receptor: multitasking in the immune system. Annu Rev Immunol 32:403–432. https://doi.org/10.1146/annurev-immunol-032713-120245
Stolt P, Bengtsson C, Nordmark B, Lindblad S, Lundberg I, Klareskog L, Alfredsson L (2003) Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases. Ann Rheum Dis 62:835–841. https://doi.org/10.1136/ard.62.9.835
Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, Ernst M et al (2007) Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 8:1363–1371. https://doi.org/10.1038/ni1537
Su HH, Lin HT, Suen JL, Sheu CC, Yokoyama KK, Huang SK, Cheng CM (2016) Aryl hydrocarbon receptor-ligand axis mediates pulmonary fibroblast migration and differentiation through increased arachidonic acid metabolism. Toxicology 370:116–126. https://doi.org/10.1016/j.tox.2016.09.019
Sung MS, Lee EG, Jeon HS, Chae HJ, Park SJ, Lee YC, Yoo WH (2012) Quercetin inhibits IL-1beta-induced proliferation and production of MMPs, COX-2, and PGE2 by rheumatoid synovial fibroblast. Inflammation 35:1585–1594. https://doi.org/10.1007/s10753-012-9473-2
Takamori M, Ide Y (1982) Effects of prostaglandin E1 in experimental autoimmune myasthenia gravis. Neurology 32:410–413. https://doi.org/10.1212/wnl.32.4.410
Tamaki A, Hayashi H, Nakajima H, Takii T, Katagiri D, Miyazawa K, Hirose K et al (2004) Polycyclic aromatic hydrocarbon increases mRNA level for interleukin 1 beta in human fibroblast-like synoviocyte line via aryl hydrocarbon receptor. Biol Pharm Bull 27:407–410
Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O (2018) Multiple sclerosis. The Lancet 391:1622–1636. https://doi.org/10.1016/s0140-6736(18)30481-1
Tomkiewicz C, Herry L, Bui LC, Metayer C, Bourdeloux M, Barouki R, Coumoul X (2013) The aryl hydrocarbon receptor regulates focal adhesion sites through a non-genomic FAK/Src pathway. Oncogene 32:1811–1820. https://doi.org/10.1038/onc.2012.197
Townsend MJ, Monroe JG, Chan AC (2010) B-cell targeted therapies in human autoimmune diseases: an updated perspective. Immunol Rev 237:264–283. https://doi.org/10.1111/j.1600-065X.2010.00945.x
Trentham DE (1982) Collagen arthritis as a relevant model for rheumatoid arthritis. Arthritis Rheum 25:911–916
Vaidyanathan B, Chaudhry A, Yewdell WT, Angeletti D, Yen WF, Wheatley AK, Bradfield CA et al (2017) The aryl hydrocarbon receptor controls cell-fate decisions in B cells. J Exp Med 214:197–208. https://doi.org/10.1084/jem.20160789
Veldhoen M, Hirota K, Christensen J, O’Garra A, Stockinger B (2009) Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J Exp Med 206:43–49. https://doi.org/10.1084/jem.20081438
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. https://doi.org/10.1038/nature06881
Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24:179–189. https://doi.org/10.1016/j.immuni.2006.01.001
Villa M, Gialitakis M, Tolaini M, Ahlfors H, Henderson CJ, Wolf CR, Brink R et al (2017) Aryl hydrocarbon receptor is required for optimal B-cell proliferation. EMBO J 36:116–128. https://doi.org/10.15252/embj.201695027
Villegas JA, Van Wassenhove J, Le Panse R, Berrih-Aknin S, Dragin N (2018) An imbalance between regulatory T cells and T helper 17 cells in acetylcholine receptor-positive myasthenia gravis patients. Ann N Y Acad Sci 1413:154–162. https://doi.org/10.1111/nyas.13591
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. https://doi.org/10.1016/j.bbrc.2008.07.156
Wagage S, John B, Krock BL, Hall AO, Randall LM, Karp CL, Simon MC et al (2014) The aryl hydrocarbon receptor promotes IL-10 production by NK cells. J Immunol 192:1661–1670. https://doi.org/10.4049/jimmunol.1300497
Wang H, Wei Y, Yu D (2015) Control of lymphocyte homeostasis and effector function by the aryl hydrocarbon receptor. Int Immunopharmacol 28:818–824. https://doi.org/10.1016/j.intimp.2015.03.046
Wang C, Ye Z, Kijlstra A, Zhou Y, Yang P (2014a) Decreased expression of the aryl hydrocarbon receptor in ocular Behcet’s disease. Mediators Inflamm 2014:195094. https://doi.org/10.1155/2014/195094
Wang C, Ye Z, Kijlstra A, Zhou Y, Yang P (2014b) Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells. Clin Exp Immunol 177:521–530. https://doi.org/10.1111/cei.12352
Wing K, Sakaguchi S (2010) Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 11:7–13. https://doi.org/10.1038/ni.1818
Wu GC, Hu Y, Guan SY, Ye DQ, Pan HF (2019) Differential plasma expression profiles of long non-coding RNAs reveal potential biomarkers for systemic lupus erythematosus. Biomolecules 9:206. https://doi.org/10.3390/biom9060206
Xuzhu G, Komai-Koma M, Leung BP, Howe HS, McSharry C, McInnes IB, Xu D (2012) Resveratrol modulates murine collagen-induced arthritis by inhibiting Th17 and B-cell function. Ann Rheum Dis 71:129–135. https://doi.org/10.1136/ard.2011.149831
Yamada T, Horimoto H, Kameyama T, Hayakawa S, Yamato H, Dazai M, Takada A et al (2016) Constitutive aryl hydrocarbon receptor signaling constrains type I interferon–mediated antiviral innate defense. Nat Immunol 17:687–694. https://doi.org/10.1038/ni.3422
Yang CM, Chen YW, Chi PL, Lin CC, Hsiao LD (2017) Resveratrol inhibits BK-induced COX-2 transcription by suppressing acetylation of AP-1 and NF-kappaB in human rheumatoid arthritis synovial fibroblasts. Biochem Pharmacol 132:77–91. https://doi.org/10.1016/j.bcp.2017.03.003
Yang D, Su Z, Wu S, Bi Y, Li X, Li J, Lou K et al (2016) Low antioxidant status of serum bilirubin, uric acid, albumin and creatinine in patients with myasthenia gravis. Int J Neurosci 126:1120–1126. https://doi.org/10.3109/00207454.2015.1134526
Yang J, Sundrud MS, Skepner J, Yamagata T (2014) Targeting Th17 cells in autoimmune diseases. Trends Pharmacol Sci 35:493–500. https://doi.org/10.1016/j.tips.2014.07.006
Ye J, Qiu J, Bostick JW, Ueda A, Schjerven H, Li S, Jobin C et al (2017) The Aryl hydrocarbon receptor preferentially marks and promotes gut regulatory T cells. Cell Rep 21:2277–2290. https://doi.org/10.1016/j.celrep.2017.10.114
Yeste A, Nadeau M, Burns EJ, Weiner HL, Quintana FJ (2012) Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 109:11270–11275. https://doi.org/10.1073/pnas.1120611109
Yeste A, Takenaka MC, Mascanfroni ID, Nadeau M, Kenison JE, Patel B, Tukpah AM et al (2016) Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2. Sci Signal 9:ra61 10.1126/scisignal.aad0612
Yu H, Jiang L, Liu R, Yang A, Yang X, Wang L, Zhang W et al (2019) Association between the ratio of aryl hydrocarbon receptor (AhR) in Th17 cells to AhR in Treg cells and SLE skin lesions. Int Immunopharmacol 69:257–262. https://doi.org/10.1016/j.intimp.2019.01.039
Yuan X, Dou Y, Wu X, Wei Z, Dai Y (2017) Tetrandrine, an agonist of aryl hydrocarbon receptor, reciprocally modulates the activities of STAT3 and STAT5 to suppress Th17 cell differentiation. J Cell Mol Med 21:2172–2183. https://doi.org/10.1111/jcmm.13141
Yuan X, Tong B, Dou Y, Wu X, Wei Z, Dai Y (2016) Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance between Th17 and Treg cells via the aryl hydrocarbon receptor. Biochem Pharmacol 101:87–99. https://doi.org/10.1016/j.bcp.2015.11.025
Zhang L, Ma J, Takeuchi M, Usui Y, Hattori T, Okunuki Y, Yamakawa N et al (2010) Suppression of experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells via activation of aryl hydrocarbon receptor. Invest Ophthalmol Vis Sci 51:2109–2117. https://doi.org/10.1167/iovs.09-3993
Zhang S, Qin C, Safe SH (2003) Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context. Environ Health Perspect 111:1877–1882. https://doi.org/10.1289/ehp.6322
Zhang LH, Shin JH, Haggadone MD, Sunwoo JB (2016) The aryl hydrocarbon receptor is required for the maintenance of liver-resident natural killer cells. J Exp Med 213:2249–2257. https://doi.org/10.1084/jem.20151998
Zhang GX, Xiao BG, Bai XF, van der Meide PH, Orn A, Link H (1999) Mice with IFN-gamma receptor deficiency are less susceptible to experimental autoimmune myasthenia gravis. J Immunol 162:3775–3781
Zhao CN, Xu Z, Wu GC, Mao YM, Liu LN, Qian W, Dan YL et al (2019) Emerging role of air pollution in autoimmune diseases. Autoimmun Rev 18:607–614. https://doi.org/10.1016/j.autrev.2018.12.010
Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W (2006) Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445:648–651. https://doi.org/10.1038/nature05505
Zhu W, Chen X, Yu J, Xiao Y, Li Y, Wan S, Su W et al (2018) Baicalin modulates the Treg/Teff balance to alleviate uveitis by activating the aryl hydrocarbon receptor. Biochem Pharmacol 154:18–27. https://doi.org/10.1016/j.bcp.2018.04.006
Acknowledgements
This study was funded by grants from the National Natural Science Foundation of China (81872687).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Wang, XS., Cao, F., Zhang, Y. et al. Therapeutic potential of aryl hydrocarbon receptor in autoimmunity. Inflammopharmacol 28, 63–81 (2020). https://doi.org/10.1007/s10787-019-00651-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-019-00651-z